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Compartmentalized DCC signalling is distinct from DCC localized to lipid rafts
Author(s) -
Petrie Ryan J.,
Zhao Beibei,
Bedford Fiona,
LamarcheVane Nathalie
Publication year - 2009
Publication title -
biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 85
eISSN - 1768-322X
pISSN - 0248-4900
DOI - 10.1042/bc20070108
Subject(s) - netrin , lipid raft , fyn , biology , microbiology and biotechnology , deleted in colorectal cancer , raft , kinase , tyrosine kinase , src family kinase , signal transduction , axon guidance , axon , cancer , chemistry , colorectal cancer , genetics , organic chemistry , copolymer , polymer
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.