Compartmentalized DCC signalling is distinct from DCC localized to lipid rafts.

Abstract:

BACKGROUND INFORMATION:Netrin-1 is a bi-functional cue that attracts or repels different classes of neurons during development. The netrin-1 receptor DCC (deleted in colorectal cancer) acts as a tyrosine kinase-associated receptor to mediate the attractive response towards netrin-1. The lipid raft-localized Src family kinase Fyn is required for DCC-mediated axon guidance. DCC functions are also dependent on lipid rafts, membrane microdomains corresponding to a low-density, detergent-resistant membrane fraction. However, it remains unclear how the association of DCC with lipid rafts controls netrin-1 signalling. RESULTS:DCC targeted to lipid rafts represented a minor proportion of total DCC inside the cell, but predominated on the cell surface of both IMR-32 human neuroblastoma cells and embryonic cortical neurons. Netrin-1 accumulated in lipid rafts, but had no effect on the targeting of DCC to that compartment, with DCC remaining on the cell surface in lipid rafts through 60 min post-treatment. However, DCC was able to interact with Fyn, both in the lipid rafts and soluble compartments isolated from embryonic E19 rat brains, whereas early downstream signalling components such as Nck-1, and total and active focal adhesion kinase were mainly localized to the non-lipid raft compartment. CONCLUSIONS:Together, these results suggest that DCC can be found in raft and non-raft portions of the plasma membrane, with early signalling events propagated by non-raft associated DCC.

journal_name

Biol Cell

journal_title

Biology of the cell

authors

Petrie RJ,Zhao B,Bedford F,Lamarche-Vane N

doi

10.1042/BC20070108

subject

Has Abstract

pub_date

2009-02-01 00:00:00

pages

77-90

issue

2

eissn

0248-4900

issn

1768-322X

pii

BC20070108

journal_volume

101

pub_type

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