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Functional Redundancy of Cyclase-Associated Proteins CAP1 and CAP2 in Differentiating Neurons

Cyclase-associated proteins (CAPs) are evolutionary-conserved actin-binding proteins with crucial functions in regulating actin dynamics, the spatiotemporally controlled assembly and disassembly of actin filaments (F-actin). Mammals possess two family members (CAP1 and CAP2) with different expressio...

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Autores principales: Schneider, Felix, Metz, Isabell, Khudayberdiev, Sharof, Rust, Marco B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234816/
https://www.ncbi.nlm.nih.gov/pubmed/34204261
http://dx.doi.org/10.3390/cells10061525
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author Schneider, Felix
Metz, Isabell
Khudayberdiev, Sharof
Rust, Marco B.
author_facet Schneider, Felix
Metz, Isabell
Khudayberdiev, Sharof
Rust, Marco B.
author_sort Schneider, Felix
collection PubMed
description Cyclase-associated proteins (CAPs) are evolutionary-conserved actin-binding proteins with crucial functions in regulating actin dynamics, the spatiotemporally controlled assembly and disassembly of actin filaments (F-actin). Mammals possess two family members (CAP1 and CAP2) with different expression patterns. Unlike most other tissues, both CAPs are expressed in the brain and present in hippocampal neurons. We recently reported crucial roles for CAP1 in growth cone function, neuron differentiation, and neuron connectivity in the mouse brain. Instead, CAP2 controls dendritic spine morphology and synaptic plasticity, and its dysregulation contributes to Alzheimer’s disease pathology. These findings are in line with a model in which CAP1 controls important aspects during neuron differentiation, while CAP2 is relevant in differentiated neurons. We here report CAP2 expression during neuron differentiation and its enrichment in growth cones. We therefore hypothesized that CAP2 is relevant not only in excitatory synapses, but also in differentiating neurons. However, CAP2 inactivation neither impaired growth cone morphology and motility nor neuron differentiation. Moreover, CAP2 mutant mice did not display any obvious changes in brain anatomy. Hence, differently from CAP1, CAP2 was dispensable for neuron differentiation and brain development. Interestingly, overexpression of CAP2 rescued not only growth cone size in CAP1-deficient neurons, but also their morphology and differentiation. Our data provide evidence for functional redundancy of CAP1 and CAP2 in differentiating neurons, and they suggest compensatory mechanisms in single mutant neurons.
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spelling pubmed-82348162021-06-27 Functional Redundancy of Cyclase-Associated Proteins CAP1 and CAP2 in Differentiating Neurons Schneider, Felix Metz, Isabell Khudayberdiev, Sharof Rust, Marco B. Cells Article Cyclase-associated proteins (CAPs) are evolutionary-conserved actin-binding proteins with crucial functions in regulating actin dynamics, the spatiotemporally controlled assembly and disassembly of actin filaments (F-actin). Mammals possess two family members (CAP1 and CAP2) with different expression patterns. Unlike most other tissues, both CAPs are expressed in the brain and present in hippocampal neurons. We recently reported crucial roles for CAP1 in growth cone function, neuron differentiation, and neuron connectivity in the mouse brain. Instead, CAP2 controls dendritic spine morphology and synaptic plasticity, and its dysregulation contributes to Alzheimer’s disease pathology. These findings are in line with a model in which CAP1 controls important aspects during neuron differentiation, while CAP2 is relevant in differentiated neurons. We here report CAP2 expression during neuron differentiation and its enrichment in growth cones. We therefore hypothesized that CAP2 is relevant not only in excitatory synapses, but also in differentiating neurons. However, CAP2 inactivation neither impaired growth cone morphology and motility nor neuron differentiation. Moreover, CAP2 mutant mice did not display any obvious changes in brain anatomy. Hence, differently from CAP1, CAP2 was dispensable for neuron differentiation and brain development. Interestingly, overexpression of CAP2 rescued not only growth cone size in CAP1-deficient neurons, but also their morphology and differentiation. Our data provide evidence for functional redundancy of CAP1 and CAP2 in differentiating neurons, and they suggest compensatory mechanisms in single mutant neurons. MDPI 2021-06-17 /pmc/articles/PMC8234816/ /pubmed/34204261 http://dx.doi.org/10.3390/cells10061525 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schneider, Felix
Metz, Isabell
Khudayberdiev, Sharof
Rust, Marco B.
Functional Redundancy of Cyclase-Associated Proteins CAP1 and CAP2 in Differentiating Neurons
title Functional Redundancy of Cyclase-Associated Proteins CAP1 and CAP2 in Differentiating Neurons
title_full Functional Redundancy of Cyclase-Associated Proteins CAP1 and CAP2 in Differentiating Neurons
title_fullStr Functional Redundancy of Cyclase-Associated Proteins CAP1 and CAP2 in Differentiating Neurons
title_full_unstemmed Functional Redundancy of Cyclase-Associated Proteins CAP1 and CAP2 in Differentiating Neurons
title_short Functional Redundancy of Cyclase-Associated Proteins CAP1 and CAP2 in Differentiating Neurons
title_sort functional redundancy of cyclase-associated proteins cap1 and cap2 in differentiating neurons
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234816/
https://www.ncbi.nlm.nih.gov/pubmed/34204261
http://dx.doi.org/10.3390/cells10061525
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