PMID- 15834419
OWN - NLM
STAT- MEDLINE
DCOM- 20050708
LR  - 20101118
IS  - 1097-6256 (Print)
IS  - 1097-6256 (Linking)
VI  - 8
IP  - 5
DP  - 2005 May
TI  - Asymmetric membrane ganglioside sialidase activity specifies axonal fate.
PG  - 606-15
AB  - Axon specification triggers the polarization of neurons and requires the 
      localized destabilization of filamentous actin. Here we show that plasma membrane 
      ganglioside sialidase (PMGS) asymmetrically accumulates at the tip of one neurite 
      of the unpolarized rat neuron, inducing actin instability. Suppressing PMGS 
      activity blocks axonal generation, whereas stimulating it accelerates the 
      formation of a single (not several) axon. PMGS induces axon specification by 
      enhancing TrkA activity locally, which triggers phosphatidylinositol-3-kinase 
      (PI3K)- and Rac1-dependent inhibition of RhoA signaling and the consequent actin 
      depolymerization in one neurite only. Thus, spatial restriction of an 
      actin-regulating molecular machinery, in this case a membrane enzymatic activity, 
      before polarization is enough to determine axonal fate.
FAU - Da Silva, Jorge Santos
AU  - Da Silva JS
AD  - Cavalieri Ottolenghi Scientific Institute, University of Turin, 10043 Orbassano, 
      Turin, Italy.
FAU - Hasegawa, Takafumi
AU  - Hasegawa T
FAU - Miyagi, Taeko
AU  - Miyagi T
FAU - Dotti, Carlos G
AU  - Dotti CG
FAU - Abad-Rodriguez, Jose
AU  - Abad-Rodriguez J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050417
PL  - United States
TA  - Nat Neurosci
JT  - Nature neuroscience
JID - 9809671
RN  - 0 (Actins)
RN  - 0 (Enzyme Inhibitors)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Receptor, trkA)
RN  - EC 3.2.1.18 (Neu3 protein, human)
RN  - EC 3.2.1.18 (Neuraminidase)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
RN  - EC 3.6.5.2 (rhoA GTP-Binding Protein)
SB  - IM
CIN - Nat Neurosci. 2005 May;8(5):544-6. PMID: 15856056
MH  - Actins/metabolism
MH  - Animals
MH  - Cell Differentiation/drug effects/*physiology
MH  - Cell Polarity/drug effects/*physiology
MH  - Cells, Cultured
MH  - Central Nervous System/cytology/*embryology/metabolism
MH  - Dendrites/drug effects/*metabolism/ultrastructure
MH  - Enzyme Inhibitors/pharmacology
MH  - Growth Cones/drug effects/*metabolism/ultrastructure
MH  - Neuraminidase/antagonists & inhibitors/*metabolism
MH  - Neurites/drug effects/metabolism/ultrastructure
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Rats
MH  - Receptor, trkA/metabolism
MH  - Signal Transduction/drug effects/physiology
MH  - rac1 GTP-Binding Protein/metabolism
MH  - rhoA GTP-Binding Protein/metabolism
EDAT- 2005/04/19 09:00
MHDA- 2005/07/09 09:00
CRDT- 2005/04/19 09:00
PHST- 2004/12/07 00:00 [received]
PHST- 2005/03/29 00:00 [accepted]
PHST- 2005/04/19 09:00 [pubmed]
PHST- 2005/07/09 09:00 [medline]
PHST- 2005/04/19 09:00 [entrez]
AID - nn1442 [pii]
AID - 10.1038/nn1442 [doi]
PST - ppublish
SO  - Nat Neurosci. 2005 May;8(5):606-15. doi: 10.1038/nn1442. Epub 2005 Apr 17.