Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

TRAK/Milton motor-adaptor proteins steer mitochondrial trafficking to axons and dendrites.

Authors: van Spronsen, Myrrhe  Mikhaylova, Marina  Lipka, Joanna  Schlager, Max A  van den Heuvel, Dave J  Kuijpers, Marijn  Wulf, Phebe S  Keijzer, Nanda  Demmers, Jeroen  Kapitein, Lukas C  Jaarsma, Dick  Gerritsen, Hans C  Akhmanova, Anna  Hoogenraad, Casper C 
Citation: van Spronsen M, etal., Neuron. 2013 Feb 6;77(3):485-502. doi: 10.1016/j.neuron.2012.11.027.
Pubmed: (View Article at PubMed) PMID:23395375
DOI: Full-text: DOI:10.1016/j.neuron.2012.11.027

In neurons, the distinct molecular composition of axons and dendrites is established through polarized targeting mechanisms, but it is currently unclear how nonpolarized cargoes, such as mitochondria, become uniformly distributed over these specialized neuronal compartments. Here, we show that TRAK family adaptor proteins, TRAK1 and TRAK2, which link mitochondria to microtubule-based motors, are required for axonal and dendritic mitochondrial motility and utilize different transport machineries to steer mitochondria into axons and dendrites. TRAK1 binds to both kinesin-1 and dynein/dynactin, is prominently localized in axons, and is needed for normal axon outgrowth, whereas TRAK2 predominantly interacts with dynein/dynactin, is more abundantly present in dendrites, and is required for dendritic development. These functional differences follow from their distinct conformations: TRAK2 preferentially adopts a head-to-tail interaction, which interferes with kinesin-1 binding and axonal transport. Our study demonstrates how the molecular interplay between bidirectional adaptor proteins and distinct microtubule-based motors drives polarized mitochondrial transport.


Gene Ontology Annotations
Objects Annotated

Additional Information

CRRD Object Information
CRRD ID: 13208834
Created: 2017-08-18
Species: All species
Last Modified: 2017-08-18
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.