HSPC300 and its role in neuronal connectivity
pmid: 17894861
pmc: PMC2098765
HSPC300 and its role in neuronal connectivity
Abstract Background The WAVE/SCAR complex, consisting of CYFIP (PIR121 or Sra1), Kette (Nap1), Abi, SCAR (WAVE) and HSPC300, is known to regulate the actin nucleating Arp2/3 complex in a Rac1-dependent manner. While in vitro and in vivo studies have demonstrated that CYFIP, Kette, Abi and SCAR work as subunits of the complex, the role of the small protein HSPC300 remains unclear. Results In the present study, we identify the HSPC300 gene and characterize its interaction with the WAVE/SCAR complex in the Drosophila animal model. On the basis of several lines of evidence, we demonstrate that HSPC300 is an indispensable component of the complex controlling axonal and neuromuscular junction (NMJ) growth. First, the Drosophila HSPC300 expression profile resembles that of other members of the WAVE/SCAR complex. Second, HSPC300 mutation, as well as mutations in the other complex subunits, results in identical axonal and NMJ growth defects. Third, like with other complex subunits, defects in NMJ architecture are rescued by presynaptic expression of the respective wild-type gene. Fourth, HSPC300 genetically interacts with another subunit of the WAVE/SCAR complex. Fifth, HSPC300 physically associates with CYFIP and SCAR. Conclusion Present data provide the first evidence for HSPC300 playing a role in nervous system development and demonstrate in vivo that this small protein works in the context of the WAVE/SCAR complex.
- Radboud University Nijmegen Medical Centre Netherlands
- French Institute of Health and Medical Research France
- University of Strasbourg France
- Emory University United States
- Radboud University Nijmegen Netherlands
PROTEIN, NCMLS 6: Genetics and epigenetic pathways of disease, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Nervous System, ACTIN DYNAMICS, SIGNALING COMPLEX, Neural Pathways, Drosophila Proteins, Developmental, 11 Medical and Health Sciences, Cells, Cultured, Cytoskeleton, Motor Neurons, Neurons, Cultured, Microfilament Proteins, Adaptor Proteins, Gene Expression Regulation, Developmental, WAVE-COMPLEX, DROSOPHILA, Drosophila melanogaster, Life Sciences & Biomedicine, RAC1, Research Article, 570, Cells, DCN 2: Functional Neurogenomics, Neuromuscular Junction, Nerve Tissue Proteins, UMCN 5.1: Genetic defects of metabolism, Developmental Neuroscience, Animals, RC346-429, Adaptor Proteins, Signal Transducing, Science & Technology, Signal Transducing, Neurosciences, SCAR ACTIVITY, SMALL GTPASE, 06 Biological Sciences, KETTE, Wiskott-Aldrich Syndrome Protein Family, Cytoskeletal Proteins, Protein Subunits, Gene Expression Regulation, Mutation, Neurosciences & Neurology, Neurology. Diseases of the nervous system, Carrier Proteins, MENTAL-RETARDATION, Developmental Biology
PROTEIN, NCMLS 6: Genetics and epigenetic pathways of disease, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Nervous System, ACTIN DYNAMICS, SIGNALING COMPLEX, Neural Pathways, Drosophila Proteins, Developmental, 11 Medical and Health Sciences, Cells, Cultured, Cytoskeleton, Motor Neurons, Neurons, Cultured, Microfilament Proteins, Adaptor Proteins, Gene Expression Regulation, Developmental, WAVE-COMPLEX, DROSOPHILA, Drosophila melanogaster, Life Sciences & Biomedicine, RAC1, Research Article, 570, Cells, DCN 2: Functional Neurogenomics, Neuromuscular Junction, Nerve Tissue Proteins, UMCN 5.1: Genetic defects of metabolism, Developmental Neuroscience, Animals, RC346-429, Adaptor Proteins, Signal Transducing, Science & Technology, Signal Transducing, Neurosciences, SCAR ACTIVITY, SMALL GTPASE, 06 Biological Sciences, KETTE, Wiskott-Aldrich Syndrome Protein Family, Cytoskeletal Proteins, Protein Subunits, Gene Expression Regulation, Mutation, Neurosciences & Neurology, Neurology. Diseases of the nervous system, Carrier Proteins, MENTAL-RETARDATION, Developmental Biology
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