PMID- 27248654
OWN - NLM
STAT- MEDLINE
DCOM- 20161226
LR  - 20230721
IS  - 2046-2441 (Electronic)
IS  - 2046-2441 (Linking)
VI  - 6
IP  - 4
DP  - 2016 Apr
TI  - ESCRT-II controls retinal axon growth by regulating DCC receptor levels and local 
      protein synthesis.
PG  - 150218
LID - 10.1098/rsob.150218 [doi]
LID - 150218
AB  - 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.
CI  - (c) 2016 The Authors.
FAU - Konopacki, Filip A
AU  - Konopacki FA
AD  - Department of Physiology Development Neuroscience, University of Cambridge, 
      Downing Street, Cambridge CB2 3DY, UK.
FAU - Wong, Hovy Ho-Wai
AU  - Wong HH
AUID- ORCID: 0000-0003-3317-478X
AD  - Department of Physiology Development Neuroscience, University of Cambridge, 
      Downing Street, Cambridge CB2 3DY, UK.
FAU - Dwivedy, Asha
AU  - Dwivedy A
AD  - Department of Physiology Development Neuroscience, University of Cambridge, 
      Downing Street, Cambridge CB2 3DY, UK.
FAU - Bellon, Anais
AU  - Bellon A
AD  - Department of Physiology Development Neuroscience, University of Cambridge, 
      Downing Street, Cambridge CB2 3DY, UK.
FAU - Blower, Michael D
AU  - Blower MD
AD  - Department of Molecular Biology, Harvard Medical School, Simches Research Center, 
      Boston, MA 02114, USA.
FAU - Holt, Christine E
AU  - Holt CE
AUID- ORCID: 0000-0003-2829-121X
AD  - Department of Physiology Development Neuroscience, University of Cambridge, 
      Downing Street, Cambridge CB2 3DY, UK ceh33@cam.ac.uk.
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - 322817/ERC_/European Research Council/International
GR  - 085314/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160420
PL  - England
TA  - Open Biol
JT  - Open biology
JID - 101580419
RN  - 0 (DCC Receptor)
RN  - 0 (DCC protein, Xenopus)
RN  - 0 (Endosomal Sorting Complexes Required for Transport)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (Xenopus Proteins)
RN  - 158651-98-0 (Netrin-1)
SB  - IM
MH  - Animals
MH  - Axons/drug effects/*metabolism
MH  - DCC Receptor
MH  - Endocytosis/drug effects
MH  - Endosomal Sorting Complexes Required for Transport/genetics/*metabolism
MH  - Endosomes/drug effects/metabolism
MH  - Gene Knockdown Techniques
MH  - Growth Cones/drug effects/metabolism
MH  - Nerve Growth Factors/pharmacology
MH  - Netrin-1
MH  - Phenotype
MH  - *Protein Biosynthesis/drug effects
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptors, Cell Surface/genetics/*metabolism
MH  - Retina/*metabolism
MH  - Retinal Ganglion Cells/drug effects/metabolism
MH  - Tumor Suppressor Proteins/pharmacology
MH  - Xenopus Proteins/genetics/*metabolism
MH  - Xenopus laevis
PMC - PMC4852451
OTO - NOTNLM
OT  - DCC
OT  - ESCRT
OT  - Netrin-1
OT  - axon guidance
OT  - endocytosis
OT  - protein synthesis
EDAT- 2016/06/02 06:00
MHDA- 2016/12/27 06:00
PMCR- 2016/04/20
CRDT- 2016/06/02 06:00
PHST- 2015/10/27 00:00 [received]
PHST- 2016/03/13 00:00 [accepted]
PHST- 2016/06/02 06:00 [entrez]
PHST- 2016/06/02 06:00 [pubmed]
PHST- 2016/12/27 06:00 [medline]
PHST- 2016/04/20 00:00 [pmc-release]
AID - rsob.150218 [pii]
AID - rsob150218 [pii]
AID - 10.1098/rsob.150218 [doi]
PST - ppublish
SO  - Open Biol. 2016 Apr;6(4):150218. doi: 10.1098/rsob.150218. Epub 2016 Apr 20.