RT Journal Article
SR Electronic
T1 Axonal transport of Hrs is activity dependent and facilitates synaptic vesicle protein degradation
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000745
DO 10.26508/lsa.202000745
VO 5
IS 10
A1 Birdsall, Veronica
A1 Kirwan, Konner
A1 Zhu, Mei
A1 Imoto, Yuuta
A1 Wilson, Scott M
A1 Watanabe, Shigeki
A1 Waites, Clarissa L
YR 2022
UL http://www.life-science-alliance.org/content/5/10/e202000745.abstract
AB Turnover of synaptic vesicle (SV) proteins is vital for the maintenance of healthy and functional synapses. SV protein turnover is driven by neuronal activity in an endosomal sorting complex required for transport (ESCRT)-dependent manner. Here, we characterize a critical step in this process: axonal transport of ESCRT-0 component Hrs, necessary for sorting proteins into the ESCRT pathway and recruiting downstream ESCRT machinery to catalyze multivesicular body (MVB) formation. We find that neuronal activity stimulates the formation of presynaptic endosomes and MVBs, as well as the motility of Hrs+ vesicles in axons and their delivery to SV pools. Hrs+ vesicles co-transport ESCRT-0 component STAM1 and comprise a subset of Rab5+ vesicles, likely representing pro-degradative early endosomes. Furthermore, we identify kinesin motor protein KIF13A as essential for the activity-dependent transport of Hrs to SV pools and the degradation of SV membrane proteins. Together, these data demonstrate a novel activity- and KIF13A-dependent mechanism for mobilizing axonal transport of ESCRT machinery to facilitate the degradation of SV membrane proteins.