Specificity and Redundancy of Profilin 1 and 2 Function in Brain Development and Neuronal Structure

Profilin functions have been discussed in numerous cellular processes, including actin polymerization. One puzzling aspect is the concomitant expression of more than one profilin isoform in most tissues. In neuronal precursors and in neurons, profilin 1 and profilin 2 are co-expressed, but their spe...

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Published inCells (Basel, Switzerland) Vol. 10; no. 9; p. 2310
Main Authors Di Domenico, Marina, Jokwitz, Melanie, Witke, Walter, Pilo Boyl, Pietro
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 03.09.2021
MDPI
Subjects
Actin
Antibodies
brain development
Cell division
Dendritic branching
Embryogenesis
Genotype & phenotype
Informatics
Isoforms
Mammals
Morphogenesis
Nervous system
Neural stem cells
neuronal branching
neuronal precursor cells
Neurons
Phenotypes
Physiology
Profilin
Stem cells
United States > US
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Abstract Profilin functions have been discussed in numerous cellular processes, including actin polymerization. One puzzling aspect is the concomitant expression of more than one profilin isoform in most tissues. In neuronal precursors and in neurons, profilin 1 and profilin 2 are co-expressed, but their specific and redundant functions in brain morphogenesis are still unclear. Using a conditional knockout mouse model to inactivate both profilins in the developing CNS, we found that threshold levels of profilin are necessary for the maintenance of the neuronal stem-cell compartment and the generation of the differentiated neurons, irrespective of the specific isoform. During embryonic development, profilin 1 is more abundant than profilin 2; consequently, modulation of profilin 1 levels resulted in a more severe phenotype than depletion of profilin 2. Interestingly, the relevance of the isoforms was reversed in the postnatal brain. Morphology of mature neurons showed a stronger dependence on profilin 2, since this is the predominant isoform in neurons. Our data highlight redundant functions of profilins in neuronal precursor expansion and differentiation, as well as in the maintenance of pyramidal neuron dendritic arborization. The specific profilin isoform is less relevant; however, a threshold profilin level is essential. We propose that the common activity of profilin 1 and profilin 2 in actin dynamics is responsible for the observed compensatory effects.
AbstractList Profilin functions have been discussed in numerous cellular processes, including actin polymerization. One puzzling aspect is the concomitant expression of more than one profilin isoform in most tissues. In neuronal precursors and in neurons, profilin 1 and profilin 2 are co-expressed, but their specific and redundant functions in brain morphogenesis are still unclear. Using a conditional knockout mouse model to inactivate both profilins in the developing CNS, we found that threshold levels of profilin are necessary for the maintenance of the neuronal stem-cell compartment and the generation of the differentiated neurons, irrespective of the specific isoform. During embryonic development, profilin 1 is more abundant than profilin 2; consequently, modulation of profilin 1 levels resulted in a more severe phenotype than depletion of profilin 2. Interestingly, the relevance of the isoforms was reversed in the postnatal brain. Morphology of mature neurons showed a stronger dependence on profilin 2, since this is the predominant isoform in neurons. Our data highlight redundant functions of profilins in neuronal precursor expansion and differentiation, as well as in the maintenance of pyramidal neuron dendritic arborization. The specific profilin isoform is less relevant; however, a threshold profilin level is essential. We propose that the common activity of profilin 1 and profilin 2 in actin dynamics is responsible for the observed compensatory effects.
Profilin functions have been discussed in numerous cellular processes, including actin polymerization. One puzzling aspect is the concomitant expression of more than one profilin isoform in most tissues. In neuronal precursors and in neurons, profilin 1 and profilin 2 are co-expressed, but their specific and redundant functions in brain morphogenesis are still unclear. Using a conditional knockout mouse model to inactivate both profilins in the developing CNS, we found that threshold levels of profilin are necessary for the maintenance of the neuronal stem-cell compartment and the generation of the differentiated neurons, irrespective of the specific isoform. During embryonic development, profilin 1 is more abundant than profilin 2; consequently, modulation of profilin 1 levels resulted in a more severe phenotype than depletion of profilin 2. Interestingly, the relevance of the isoforms was reversed in the postnatal brain. Morphology of mature neurons showed a stronger dependence on profilin 2, since this is the predominant isoform in neurons. Our data highlight redundant functions of profilins in neuronal precursor expansion and differentiation, as well as in the maintenance of pyramidal neuron dendritic arborization. The specific profilin isoform is less relevant; however, a threshold profilin level is essential. We propose that the common activity of profilin 1 and profilin 2 in actin dynamics is responsible for the observed compensatory effects.
Author Di Domenico, Marina
Pilo Boyl, Pietro
Jokwitz, Melanie
Witke, Walter
AuthorAffiliation Institute of Genetics, University of Bonn, 53115 Bonn, Germany; marinadidomenico@gmail.com (M.D.D.); mjokwitz@uni-bonn.de (M.J.); w.witke@uni-bonn.de (W.W.)
AuthorAffiliation_xml – name: Institute of Genetics, University of Bonn, 53115 Bonn, Germany; marinadidomenico@gmail.com (M.D.D.); mjokwitz@uni-bonn.de (M.J.); w.witke@uni-bonn.de (W.W.)
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Snippet Profilin functions have been discussed in numerous cellular processes, including actin polymerization. One puzzling aspect is the concomitant expression of...
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StartPage 2310
SubjectTerms Actin
Antibodies
brain development
Cell division
Dendritic branching
Embryogenesis
Genotype & phenotype
Informatics
Isoforms
Mammals
Morphogenesis
Nervous system
Neural stem cells
neuronal branching
neuronal precursor cells
Neurons
Phenotypes
Physiology
Profilin
Stem cells
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Title Specificity and Redundancy of Profilin 1 and 2 Function in Brain Development and Neuronal Structure
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https://pubmed.ncbi.nlm.nih.gov/PMC8467068
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