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Compartmentalized DCC signalling is distinct from DCC localized to lipid rafts
Journal article   Open access   Peer reviewed

Compartmentalized DCC signalling is distinct from DCC localized to lipid rafts

Ryan J. Petrie, Beibei Zhao, Fiona Bedford and Nathalie Lamarche-Vane
Biology of the cell, v 101(2), pp 77-90
01 Feb 2009
PMID: 18616430
url
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1042/BC20070108View
Published, Version of Record (VoR) Open
url
https://doi.org/10.1042/BC20070108View
Published, Version of Record (VoR) Open

Abstract

Cell Biology Life Sciences & Biomedicine Science & Technology
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 El 9 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.

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