Retrolinkin, a membrane protein, plays an important role in retrograde axonal transport.
Retrograde axonal transport plays an important role in the maintenance of neuronal functions, but the mechanism is poorly defined partly because the constituents of the retrograde transport system and their interactions have yet to be elucidated. Of special interest is how dynein/dynactin motor proteins interact with membrane cargoes. Here, we report that an endosomal vesicle protein, termed retrolinkin, functions as a receptor tethering vesicles to dynein/dynactin through BPAG1n4. Retrolinkin, a membrane protein highly enriched in neuronal endosomes, binds directly to BPAG1n4. Deletion of retrolinkin membrane-association domains disrupts retrograde vesicular transport, recapitulating the BPAG1 null phenotype. We propose that retrolinkin acts with BPAG1n4 to specifically regulate retrograde axonal transport. Our work lays the foundation for understanding fundamental issues of axonal transport and provides insights into the molecular mechanisms underlying human neurodegenerative disorders.
Liu
Jia-Jia
JJ
Department of Neurology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Ding
Jianqing
J
Wu
Chengbiao
C
Bhagavatula
Prasanthi
P
Cui
Bianxiao
B
Chu
Steve
S
Mobley
William C
WC
Yang
Yanmin
Y
D000818:Animals; D001370:Axonal Transport; D002352:Carrier Proteins / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism; D000071821:Dystonin; D011992:Endosomes / Q000378:metabolism; D007425:Intracellular Membranes / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D020409:Molecular Motor Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D033921:Vesicular Transport Proteins / Q000378:metabolism / Q000502:physiology
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C095667:Dst protein, mouse; D000072159:Dynactin Complex; D000071821:Dystonin; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D020409:Molecular Motor Proteins; D009419:Nerve Tissue Proteins; D033921:Vesicular Transport Proteins; D004398:Dyneins