Role of Tropomodulin’s Leucine Rich Repeat Domain in the Formation of Neurite-like Processes

Laurent Guillaud; Kevin T Gray; Natalia Moroz; Caroline Pantazis; Edward Pate; Alla S Kostyukova

doi:10.1021/bi401431k

Back

Role of Tropomodulin’s Leucine Rich Repeat Domain in the Formation of Neurite-like Processes

Journal article

Open access

Peer reviewed

Role of Tropomodulin’s Leucine Rich Repeat Domain in the Formation of Neurite-like Processes

Laurent Guillaud, Kevin T Gray, Natalia Moroz, Caroline Pantazis, Edward Pate and Alla S Kostyukova

Biochemistry (Easton), Vol.53(16), pp.2689-2700

04/29/2014

DOI: https://doi.org/10.1021/bi401431k

Handle:

https://hdl.handle.net/2376/106793

PMCID: PMC4018078

PMID: 24746171

Files and links (1)

url

https://doi.org/10.1021/bi401431kView

Published (Version of record) Open

Abstract

Actin dynamics is fundamental for neurite development; monomer depolymerization from pointed ends is rate-limiting in actin treadmilling. Tropomodulins (Tmod) make up a family of actin pointed end-capping proteins. Of the four known isoforms, Tmod1–Tmod3 are expressed in brain cells. We investigated the role of Tmod’s C-terminal (LRR) domain in the formation of neurite-like processes by overexpressing Tmod1 and Tmod2 with deleted or mutated LRR domains in PC12 cells, a model system used to study neuritogenesis. Tmod1 overexpression results in a normal quantity and a normal length of processes, while Tmod2 overexpression reduces both measures. The Tmod2 overexpression phenotype is mimicked by overexpression of Tmod1 with the LRR domain removed or with three point mutations in the LRR domain that disrupt exposed clusters of conserved residues. Removal of Tmod2’s LRR domain does not significantly alter the outgrowth of neurite-like processes compared to that of Tmod2. Overexpression of chimeras with the N-terminal and C-terminal domains switched between Tmod1 and Tmod2 reinforces the idea that Tmod1’s LRR domain counteracts the reductive effect of the Tmod N-terminal domain upon formation of processes while Tmod2’s LRR domain does not. We suggest that the TM-dependent actin capping ability of both Tmods inhibits the formation of processes, but in Tmod1, this inhibition can be controlled via its LRR domain. Circular dichroism, limited proteolysis, and molecular dynamics demonstrate structural differences in the C-terminal region of the LRR domains of Tmod1, Tmod2, and the Tmod1 mutant.

Metrics

6 Record Views

Details

Title: Role of Tropomodulin’s Leucine Rich Repeat Domain in the Formation of Neurite-like Processes
Creators: Laurent Guillaud - Cellular and Molecular Synaptic Function Unit
Kevin T Gray - Voiland School of Chemical Engineering and Bioengineering
Natalia Moroz - Voiland School of Chemical Engineering and Bioengineering
Caroline Pantazis - Department of Neuroscience and Cell Biology
Edward Pate - Voiland School of Chemical Engineering and Bioengineering
Alla S Kostyukova - Voiland School of Chemical Engineering and Bioengineering
Publication Details: Biochemistry (Easton), Vol.53(16), pp.2689-2700
Academic Unit: Chemical Engineering and Bioengineering, School of
Publisher: American Chemical Society
Identifiers: 99900546773801842
Language: English
Resource Type: Journal article