Mutations changing tropomodulin affinity for tropomyosin alter neurite formation and extension

Natalia Moroz; Laurent Guillaud; Brinda Desai; Alla S Kostyukova

doi:10.7717/peerj.7

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Mutations changing tropomodulin affinity for tropomyosin alter neurite formation and extension

Journal article

Open access

Peer reviewed

Mutations changing tropomodulin affinity for tropomyosin alter neurite formation and extension

Natalia Moroz, Laurent Guillaud, Brinda Desai and Alla S Kostyukova

PeerJ (San Francisco, CA), Vol.1(1), pp.e7-e7

2013

DOI: https://doi.org/10.7717/peerj.7

Handle:

https://hdl.handle.net/2376/108290

PMCID: PMC3628370

PMID: 23638401

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Abstract

Neuroscience

Molecular Biology

Tropomyosin

Actin

Tropomodulin

Cytoskeleton

Neurite formation

Cell Biology

Assembly of the actin cytoskeleton is an important part of formation of neurites in developing neurons. Tropomodulin, a tropomyosin-dependent capping protein for the pointed end of the actin filament, is one of the key players in this process. Tropomodulin binds tropomyosin in two binding sites. Tmod1 and Tmod2, tropomodulin isoforms found in neurons, were overexpressed in PC12 cells, a model system for neuronal differentiation. Tmod1 did not affect neuronal differentiation; while cells expressing Tmod2 showed a significant reduction in the number and the length of neurites. Both tropomodulins bind short α-, γ- and δ-tropomyosin isoforms. Mutations in one of the tropomyosin-binding sites of Tmod1, which increased its affinity to short γ- and δ-tropomyosin isoforms, caused a decrease in binding short α-tropomyosin isoforms along with a 2-fold decrease in the length of neurites. Our data demonstrate that Tmod1 is involved in neuronal differentiation for proper neurite formation and outgrowth, and that Tmod2 inhibits these processes. The mutations in the tropomyosin-binding site of Tmod1 impair neurite outgrowth, suggesting that the integrity of this binding site is critical for the proper function of Tmod1 during neuronal differentiation.

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Title: Mutations changing tropomodulin affinity for tropomyosin alter neurite formation and extension
Creators: Natalia Moroz - ,
Laurent Guillaud - ,
Brinda Desai - ,
Alla S Kostyukova - ,
Publication Details: PeerJ (San Francisco, CA), Vol.1(1), pp.e7-e7
Academic Unit: Chemical Engineering and Bioengineering, School of
Publisher: PeerJ Inc; San Francisco, USA
Grant note: GM081688 / National Institutes of Health grant
Identifiers: 99900546825101842
Language: English
Resource Type: Journal article