|ZFIN ID: ZDB-PUB-200814-11|
A Conserved Role for Vezatin Proteins in Cargo-Specific Regulation of Retrograde Axonal Transport
Spinner, M.A., Pinter, K., Drerup, C.M., Herman, T.G.
|Source:||Genetics 216(2): 431-445 (Journal)|
|Registered Authors:||Drerup, Katie (Catherine)|
|Keywords:||Diamond, Vezatin, axonal transport, endosome, retrograde|
|PubMed:||32788307 Full text @ Genetics|
Spinner, M.A., Pinter, K., Drerup, C.M., Herman, T.G. (2020) A Conserved Role for Vezatin Proteins in Cargo-Specific Regulation of Retrograde Axonal Transport. Genetics. 216(2):431-445.
ABSTRACTActive transport of organelles within axons is critical for neuronal health. Retrograde axonal transport, in particular, relays neurotrophic signals received by axon terminals to the nucleus and circulates new material among en passant synapses. A single motor protein complex, cytoplasmic dynein, is responsible for nearly all retrograde transport within axons: its linkage to and transport of diverse cargos is achieved by cargo-specific regulators. Here we identify Vezatin as a conserved regulator of retrograde axonal transport. Vertebrate Vezatin (Vezt) is required for the maturation and maintenance of cell-cell junctions and has not previously been implicated in axonal transport. However, a related fungal protein, VezA, has been shown to regulate retrograde transport of endosomes in hyphae. In a forward genetic screen, we identified a loss-of-function mutation in the Drosophilavezatin-like (vezl) gene. We here show that vezl loss prevents a subset of endosomes, including signaling endosomes containing activated BMP receptors, from initiating transport out of motor neuron terminal boutons. vezl loss also decreases the transport of endosomes and dense core vesicles (DCVs) but not mitochondria within axon shafts. We disrupted vezt in zebrafish and found that vezt loss specifically impairs the retrograde axonal movement of late endosomes, causing their accumulation in axon terminals. Our work establishes a conserved, cargo-specific role for Vezatin proteins in retrograde axonal transport.