How neurons regulate transport on the microtubule highway system.
or technically,
alpha-Tubulin Tyrosination and CLIP-170 Phosphorylation Regulate the Initiation of Dynein-Driven Transport in Neurons.
[See Original Abstract on Pubmed]
Authors of the study: Jeffrey J. Nirschl, Maria M. Magiera, Jacob E. Lazarus, Carsten Janke, Erika L.F. Holzbaur
The longest neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles in the human body are the motor neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles that help you wiggle your toes. These neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles extend long branches, called axonsA specialized part of a neuron that sends electrical and chemical signals to other cells. Axons are typically long and thin like a wire., that travel from the spinal cord in your lower back all the way down to your toes. These axonsA specialized part of a neuron that sends electrical and chemical signals to other cells. Axons are typically long and thin like a wire. are often a few feet long (maybe even longer if you’re a professional basketball player like Shaquille O’Neal)! To maintain the ability to wiggle your toes, these neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles need to be able to transport important molecules down the entire length of their axonA specialized part of a neuron that sends electrical and chemical signals to other cells. Axons are typically long and thin like a wire.. Thankfully, all neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles have a highway system made of microtubulesMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. (which is just a fancy scientific way to say “tiny tubes”) that they can use to transport molecules down their axonsA specialized part of a neuron that sends electrical and chemical signals to other cells. Axons are typically long and thin like a wire.. A proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. called dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell.
walks along these microtubulesMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. and carries other molecules or “cargo” with it. In this way, dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell.
is like a truck that pulls trailers throughout the neuronA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles on the microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway system. These trailers contain specific cargo that the neuronA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles needs in different places.
NeuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles need to maintain tight control over what gets transported on this microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway system. They do this by modifying proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. that attach the dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. motor proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. to the microtubulesMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization.. You can think of these proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. as traffic conductors controlling which cars (and therefore what cargo) get onto the highway. NeuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles throughout the body need to be able to control when and where dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. gets onto the microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway and what cargo it is carrying. Scientists know that when neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles lose control of the microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway system, it can cause problems and may even result in neurological disorders like Parkinson’s Disease. But how the cell regulates dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. is not yet understood. Jeffrey Nirschl, a neuroscience graduate student at the University of Pennsylvania in Erika Holzbaur’s lab, was interested in figuring out how neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles regulate dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell.
. DyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. can be placed onto the microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway by specific proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. in the cell such as CLIP-170 (you can remember that it “clips” dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. onto the microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway). Jeffrey thought that CLIP-170 was the key player in regulating when and where dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. gets “clipped” onto the microtubulesMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization.. The cool thing about CLIP-170 is that it has a brake mechanism, called a phosphorylationA post-translational protein modification in which a phosphate group is added to alter the activity or location of proteins within the cell. tag, that prevents CLIP-170 from attaching dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. to the microtubulesMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization.. When this phosphorylationA post-translational protein modification in which a phosphate group is added to alter the activity or location of proteins within the cell. tag is removed (or when CLIP-170 is dephosphorylated), CLIP-170 is activated. In other words, removal of the brake on CLIP-170 allows it to clip dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. onto microtubulesMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization.. Through his work, Jeffrey discovered that the CLIP-170 regulates when dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. is attached to the microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway.
Jeffrey also hypothesized that the microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway itself could be modified to regulate when and where dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. can get on the highway, much like traffic cones regulate where cars can go. Tubulin is the proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. building block of microtubulesMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization.. Many tubulin proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. come together and bind end-to-end to form long (but tiny) tubes that run the entire length of the axonA specialized part of a neuron that sends electrical and chemical signals to other cells. Axons are typically long and thin like a wire.. Modification of tubulin building blocks changes the structure and function of the microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway. One way in which the highway can be modified is called tyrosinationA post-translational protein modification in which the amino acid tyrosine is added to the protein to alter its function., in which the amino acid tyrosine is reversibly added to the tubulin making up the microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway. The process of tyrosinationA post-translational protein modification in which the amino acid tyrosine is added to the protein to alter its function. can be thought of as road workers putting cones on the highway during construction periods. But unlike traffic cones, tyrosinationA post-translational protein modification in which the amino acid tyrosine is added to the protein to alter its function. increases the ability of dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. to get on the highway and transport its cargo. Jeffrey was able to demonstrate that microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. tyrosinationA post-translational protein modification in which the amino acid tyrosine is added to the protein to alter its function. regulates where dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. is put onto the microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway.
By looking at living neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles and proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies., Jeffrey showed that CLIP-170 regulates when dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. gets on the microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway and microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. tyrosinationA post-translational protein modification in which the amino acid tyrosine is added to the protein to alter its function. determines where dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. gets on the highway. This allows neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles to control the location of proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. and molecules in the neuronA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles in time and space so it can always function. We are grateful the motor neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles running all the way from our lower back to our toes can do this so we can wiggle our toes every morning.
NeuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles need to maintain tight control over what gets transported on this microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway system. They do this by modifying proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. that attach the dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. motor proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. to the microtubulesMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization.. You can think of these proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. as traffic conductors controlling which cars (and therefore what cargo) get onto the highway. NeuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles throughout the body need to be able to control when and where dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. gets onto the microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway and what cargo it is carrying. Scientists know that when neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles lose control of the microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway system, it can cause problems and may even result in neurological disorders like Parkinson’s Disease. But how the cell regulates dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. is not yet understood. Jeffrey Nirschl, a neuroscience graduate student at the University of Pennsylvania in Erika Holzbaur’s lab, was interested in figuring out how neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles regulate dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell.
. DyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. can be placed onto the microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway by specific proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. in the cell such as CLIP-170 (you can remember that it “clips” dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. onto the microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway). Jeffrey thought that CLIP-170 was the key player in regulating when and where dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. gets “clipped” onto the microtubulesMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization.. The cool thing about CLIP-170 is that it has a brake mechanism, called a phosphorylationA post-translational protein modification in which a phosphate group is added to alter the activity or location of proteins within the cell. tag, that prevents CLIP-170 from attaching dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. to the microtubulesMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization.. When this phosphorylationA post-translational protein modification in which a phosphate group is added to alter the activity or location of proteins within the cell. tag is removed (or when CLIP-170 is dephosphorylated), CLIP-170 is activated. In other words, removal of the brake on CLIP-170 allows it to clip dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. onto microtubulesMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization.. Through his work, Jeffrey discovered that the CLIP-170 regulates when dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. is attached to the microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway.
Jeffrey also hypothesized that the microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway itself could be modified to regulate when and where dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. can get on the highway, much like traffic cones regulate where cars can go. Tubulin is the proteinAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. building block of microtubulesMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization.. Many tubulin proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. come together and bind end-to-end to form long (but tiny) tubes that run the entire length of the axonA specialized part of a neuron that sends electrical and chemical signals to other cells. Axons are typically long and thin like a wire.. Modification of tubulin building blocks changes the structure and function of the microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway. One way in which the highway can be modified is called tyrosinationA post-translational protein modification in which the amino acid tyrosine is added to the protein to alter its function., in which the amino acid tyrosine is reversibly added to the tubulin making up the microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway. The process of tyrosinationA post-translational protein modification in which the amino acid tyrosine is added to the protein to alter its function. can be thought of as road workers putting cones on the highway during construction periods. But unlike traffic cones, tyrosinationA post-translational protein modification in which the amino acid tyrosine is added to the protein to alter its function. increases the ability of dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. to get on the highway and transport its cargo. Jeffrey was able to demonstrate that microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. tyrosinationA post-translational protein modification in which the amino acid tyrosine is added to the protein to alter its function. regulates where dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. is put onto the microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway.
By looking at living neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles and proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies., Jeffrey showed that CLIP-170 regulates when dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. gets on the microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. highway and microtubuleMicroscopic tubular structures in the cells made of the protein tubulin that form a skeleton or highway system to help the cell maintain structure and organization. tyrosinationA post-translational protein modification in which the amino acid tyrosine is added to the protein to alter its function. determines where dyneinA motor protein that moves along microtubules and helps carry cargo to various parts of the cell. gets on the highway. This allows neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles to control the location of proteinsAn essential molecule found in all cells. DNA contains the recipes the cell uses to make proteins. Examples of proteins include receptors, enzymes, and antibodies. and molecules in the neuronA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles in time and space so it can always function. We are grateful the motor neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles running all the way from our lower back to our toes can do this so we can wiggle our toes every morning.
About the brief writer: Rachel Cerón
Rachel is a PhD Candidate co-mentored by Robert Heuckeroth and Roberto Dominguez. She is studying molecular mechanisms that underlie human diseases in the gastrointestinal system including those that affect the enteric nervous system (the brain in your gut).