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Current Biology
Article
License: Elsevier Non-Commercial
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Current Biology
Article . 2012
License: Elsevier Non-Commercial
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Current Biology
Article . 2012 . Peer-reviewed
License: Elsevier Non-Commercial
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The F-BAR Protein CIP4 Inhibits Neurite Formation by Producing Lamellipodial Protrusions

Authors: Saengsawang, Witchuda; Mitok, Kelly; Viesselmann, Chris; Pietila, Lauren; Lumbard, Derek C.; Corey, Seth J.; Dent, Erik W.;

The F-BAR Protein CIP4 Inhibits Neurite Formation by Producing Lamellipodial Protrusions

Abstract

Neurite formation is a seminal event in the early development of neurons. However, little is known about the mechanisms by which neurons form neurites. F-BAR proteins function in sensing and inducing membrane curvature. Cdc42-interacting protein 4 (CIP4), a member of the F-BAR family, regulates endocytosis in a variety of cell types. However, there is little data on how CIP4 functions in neurons. Here we show that CIP4 plays a novel role in neuronal development by inhibiting neurite formation. Remarkably, CIP4 exerts this effect not through endocytosis, but by producing lamellipodial protrusions. In primary cortical neurons CIP4 is concentrated specifically at the tips of extending lamellipodia and filopodia, instead of endosomes as in other cell types. Overexpression of CIP4 results in lamellipodial protrusions around the cell body, subsequently delaying neurite formation and enlarging growth cones. These effects depend on the F-BAR and SH3 domains of CIP4 and on its ability to multimerize. Conversely, cortical neurons from CIP4-null mice initiate neurites twice as fast as controls. This is the first study to demonstrate that an F-BAR protein functions differently in neuronal versus nonneuronal cells and induces lamellipodial protrusions instead of invaginations or filopodia-like structures.

Keywords

Cerebral Cortex, Mice, Knockout, Neurons, Agricultural and Biological Sciences(all), Biochemistry, Genetics and Molecular Biology(all), Neurogenesis, Recombinant Fusion Proteins, Endocytosis, Minor Histocompatibility Antigens, src Homology Domains, Mice, COS Cells, Chlorocebus aethiops, Neurites, Animals, Pseudopodia, Protein Multimerization, Microtubule-Associated Proteins, Cells, Cultured

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
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    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
Powered by OpenAIRE graph
citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
46
Top 10%
Top 10%
Top 10%
hybrid