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XB-ART-52527
Open Biol April 1, 2016; 6 (4): 150218.
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ESCRT-II controls retinal axon growth by regulating DCC receptor levels and local protein synthesis.

Konopacki FA , Wong HH , Dwivedy A , Bellon A , Blower MD , Holt CE .


Abstract
Endocytosis and local protein synthesis (LPS) act coordinately to mediate the chemotropic responses of axons, but the link between these two processes is poorly understood. The endosomal sorting complex required for transport (ESCRT) is a key regulator of cargo sorting in the endocytic pathway, and here we have investigated the role of ESCRT-II, a critical ESCRT component, in Xenopus retinal ganglion cell (RGC) axons. We show that ESCRT-II is present in RGC axonal growth cones (GCs) where it co-localizes with endocytic vesicle GTPases and, unexpectedly, with the Netrin-1 receptor, deleted in colorectal cancer (DCC). ESCRT-II knockdown (KD) decreases endocytosis and, strikingly, reduces DCC in GCs and leads to axon growth and guidance defects. ESCRT-II-depleted axons fail to turn in response to a Netrin-1 gradient in vitro and many axons fail to exit the eye in vivo These defects, similar to Netrin-1/DCC loss-of-function phenotypes, can be rescued in whole (in vitro) or in part (in vivo) by expressing DCC. In addition, ESCRT-II KD impairs LPS in GCs and live imaging reveals that ESCRT-II transports mRNAs in axons. Collectively, our results show that the ESCRT-II-mediated endocytic pathway regulates both DCC and LPS in the axonal compartment and suggest that ESCRT-II aids gradient sensing in GCs by coupling endocytosis to LPS.

PubMed ID: 27248654
PMC ID: PMC4852451
Article link: Open Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: dcc rab11a rab5a rab7a rpl5 snf8 tec ugcg vps25 vps36
Morpholinos: vps25 MO1 vps25 MO2


Article Images: [+] show captions
References [+] :
Allison, An ESCRT-spastin interaction promotes fission of recycling tubules from the endosome. 2013, Pubmed