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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MDPI AG
2021-06-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/6/1525 |
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| author | Felix Schneider Isabell Metz Sharof Khudayberdiev Marco B. Rust |
| author_facet | Felix Schneider Isabell Metz Sharof Khudayberdiev Marco B. Rust |
| author_sort | Felix Schneider |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T10:20:46Z |
| format | Article |
| id | doaj.art-b64f57318e134f5db3336c652c9605a2 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T10:20:46Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-b64f57318e134f5db3336c652c9605a22023-11-22T00:28:28ZengMDPI AGCells2073-44092021-06-01106152510.3390/cells10061525Functional Redundancy of Cyclase-Associated Proteins CAP1 and CAP2 in Differentiating NeuronsFelix Schneider0Isabell Metz1Sharof Khudayberdiev2Marco B. Rust3Molecular Neurobiology Group, Institute of Physiological Chemistry, University of Marburg, 35032 Marburg, GermanyMolecular Neurobiology Group, Institute of Physiological Chemistry, University of Marburg, 35032 Marburg, GermanyMolecular Neurobiology Group, Institute of Physiological Chemistry, University of Marburg, 35032 Marburg, GermanyMolecular Neurobiology Group, Institute of Physiological Chemistry, University of Marburg, 35032 Marburg, GermanyCyclase-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.https://www.mdpi.com/2073-4409/10/6/1525cyclase-associated proteinCAP2CAP1SRV2growth coneactin dynamics |
| spellingShingle | Felix Schneider Isabell Metz Sharof Khudayberdiev Marco B. Rust Functional Redundancy of Cyclase-Associated Proteins CAP1 and CAP2 in Differentiating Neurons Cells cyclase-associated protein CAP2 CAP1 SRV2 growth cone actin dynamics |
| 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 | cyclase-associated protein CAP2 CAP1 SRV2 growth cone actin dynamics |
| url | https://www.mdpi.com/2073-4409/10/6/1525 |
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