PMID- 10399920
OWN - NLM
STAT- MEDLINE
DCOM- 19990729
LR  - 20190705
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 97
IP  - 7
DP  - 1999 Jun 25
TI  - A ligand-gated association between cytoplasmic domains of UNC5 and DCC family
      receptors converts netrin-induced growth cone attraction to repulsion.
PG  - 927-41
AB  - Netrins are bifunctional: they attract some axons and repel others. Netrin
      receptors of the Deleted in Colorectal Cancer (DCC) family are implicated in
      attraction and those of the UNC5 family in repulsion, but genetic evidence also
      suggests involvement of the DCC protein UNC-40 in some cases of repulsion. To
      test whether these proteins form a receptor complex for repulsion, we studied the
      attractive responses of Xenopus spinal axons to netrin-1, which are mediated by
      DCC. We show that attraction is converted to repulsion by expression of UNC5
      proteins in these cells, that this repulsion requires DCC function, that the UNC5
      cytoplasmic domain is sufficient to effect the conversion, and that repulsion can
      be initiated by netrin-1 binding to either UNC5 or DCC. The isolated cytoplasmic 
      domains of DCC and UNC5 proteins interact directly, but this interaction is
      repressed in the context of the full-length proteins. We provide evidence that
      netrin-1 triggers the formation of a receptor complex of DCC and UNC5 proteins
      and simultaneously derepresses the interaction between their cytoplasmic domains,
      thereby converting DCC-mediated attraction to UNC5/DCC-mediated repulsion.
FAU - Hong, K
AU  - Hong K
AD  - Department of Biology, University of California, San Diego, 92093, USA.
FAU - Hinck, L
AU  - Hinck L
FAU - Nishiyama, M
AU  - Nishiyama M
FAU - Poo, M M
AU  - Poo MM
FAU - Tessier-Lavigne, M
AU  - Tessier-Lavigne M
FAU - Stein, E
AU  - Stein E
LA  - eng
GR  - NS22764/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Caenorhabditis elegans Proteins)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (DCC Receptor)
RN  - 0 (Dcc protein, mouse)
RN  - 0 (Helminth Proteins)
RN  - 0 (Ligands)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Netrin Receptors)
RN  - 0 (Ntn1 protein, mouse)
RN  - 0 (Ntn1 protein, rat)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Growth Factor)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 149592-60-9 (UNC-5 protein, C elegans)
RN  - 158651-98-0 (Netrin-1)
SB  - IM
CIN - Cell. 1999 Jun 25;97(7):821-4. PMID: 10399909
MH  - Amino Acid Sequence
MH  - Animals
MH  - Axons/*physiology
MH  - Binding Sites
MH  - COS Cells
MH  - *Caenorhabditis elegans Proteins
MH  - Cell Adhesion Molecules/*metabolism
MH  - Cell Line
MH  - Cytoplasm/metabolism
MH  - DCC Receptor
MH  - Growth Cones/physiology
MH  - Helminth Proteins/genetics/*metabolism
MH  - Ligands
MH  - Membrane Proteins/genetics/*metabolism
MH  - Mice
MH  - Molecular Sequence Data
MH  - Nerve Growth Factors/metabolism
MH  - Netrin Receptors
MH  - Netrin-1
MH  - Rats
MH  - Receptors, Cell Surface/genetics/*metabolism
MH  - Receptors, Growth Factor/genetics/*metabolism
MH  - *Tumor Suppressor Proteins
MH  - Xenopus/embryology
EDAT- 1999/07/10 00:00
MHDA- 1999/07/10 00:01
CRDT- 1999/07/10 00:00
PHST- 1999/07/10 00:00 [pubmed]
PHST- 1999/07/10 00:01 [medline]
PHST- 1999/07/10 00:00 [entrez]
AID - S0092-8674(00)80804-1 [pii]
AID - 10.1016/s0092-8674(00)80804-1 [doi]
PST - ppublish
SO  - Cell. 1999 Jun 25;97(7):927-41. doi: 10.1016/s0092-8674(00)80804-1.