Alternative splicing variations in mouse CAPS2: differential expression and functional properties of splicing variants

abstract: ...Background Ca 2+ -dependent activator protein 2 (CAPS2/CADPS2) is a secretory vesicle-associated protein involved in the release of neurotrophin. We recently reported that an aberrant, alternatively spliced CAPS2 mRNA that lacks exon 3 (CAPS2exon3) is detected in some patients with autism. Splicing variations in mouse CAPS2 and their expression and functions remain unclear. Results In this study, we defined 31 exons in the mouse CAPS2 gene and identified six alternative splicing variants, CAPS2a-f. CAPS2a is an isoform lacking exons 22 and 25, which encode part of the Munc13-1-homologous domain (MHD). CAPS2b lacks exon 25. CAPS2c lacks exons 11 and 22. CAPS2d, 2e, and 2f have C-terminal deletions from exon 14, exon 12, and exon 5, respectively. On the other hand, a mouse counterpart of CAPS2exon3 was not detected in the mouse tissues tested. CAPS2b was expressed exclusively in the brain, and the other isoforms were highly expressed in the brain, but also in some non-neural tissues. In the brain, all isoforms showed predominant expression patterns in the cerebellum. In the developing cerebellum, CAPS2b showed an up-regulated expression pattern, whereas the other isoforms exhibited transiently peaked expression patterns. CAPS2 proteins were mostly recovered in soluble fractions, but some were present in membrane fractions, except for CAPS2c and 2f, both of which lack the PH domain, suggesting that the PH domain is important for membrane association. In contrast to CAPS2a and 2b, CAPS2c showed slightly decreased BDNF-releasing activity, which is likely due to the C-terminal truncation of the PH domain in CAPS2c. Conclusion This study indicates that, in mouse, there are six splicing variants of CAPS2 (CAPS2a-f), and that these are subdivided into two groups: a long form containing the C-terminal MHD and a short form lacking the C-terminal MHD. These results demonstrate that the splicing variations correlate with their expression patterns and intracellular distribution, and affect BDNF release; however, whether or not the short forms possess activities other than BDNF release, for example as natural dominant-negative isoforms, remains to be determined.

...BMC Neurosci BMC Neuroscience 1471-2202 BioMed Central London 17428348 1853102 1471-2202-8-25 10.1186/1471-2202-8-25 Research Article Alternative splicing variations in mouse CAPS2: differential expression and functional properties of splicing variants Sadakata Tetsushi 1 sadakata@brain.riken.go.jp Washida Miwa 1 m-washida@brain.riken.jp Furuichi Teiichi 1 tfuruichi@brain.riken.jp 1 Laboratory for Molecular Neurogenesis, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan 2007 12 4 2007 8 25 25 9 2 2007 12 4 2007 Copyright 2007 Sadakata et al; licensee BioMed Central Ltd. 2007 Sadakata et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background Ca 2+ -dependent activator protein 2 (CAPS2/CADPS2) is a secretory vesicle-associated protein involved in the release of neurotrophin. We recently reported that an aberrant, alternatively spliced CAPS2 mRNA that lacks exon 3 (CAPS2exon3) is detected in some patients with autism. Splicing variations in mouse CAPS2 and their expression and functions remain unclear. Results In this study, we defined 31 exons in the mouse CAPS2 gene and identified six alternative splicing variants, CAPS2a-f. CAPS2a is an isoform lacking exons 22 and 25, which encode part of the Munc13-1-homologous domain (MHD). CAPS2b

... showed an up-regulated expression pattern, whereas the other isoforms exhibited transiently peaked expression patterns. CAPS2 proteins were mostly recovered in soluble fractions, but some were present in membrane fractions, except for CAPS2c and 2f, both of which lack the PH domain, suggesting that the PH domain is important for membrane association. In contrast to CAPS2a and 2b, CAPS2c showed slightly decreased BDNF-releasing activity, which is likely due to the C-terminal truncation of the PH domain in CAPS2c. Conclusion This study indicates that, in mouse, there are six splicing variants of CAPS2 (CAPS2a-f), and that these are subdivided into two groups: a long form containing the C-terminal MHD and a short form lacking the C-terminal MHD. These results demonstrate that the splicing variations correlate with their expression patterns and intracellular distribution, and affect BDNF release; however, whether or not the short forms possess activities other than BDNF release, for example as natural dominant-negative isoforms, remains to be determined. Background The Ca 2+ -dependent activator protein for secretion (CAPS/CADPS) family consists of two members, CAPS1/CADPS1 [ 1 - 3 ] and CAPS2/CADPS2 [ 4 - 6 ]. CAPS1 was shown to play a role in the ATP-dependent priming step of Ca 2+ -triggered dense-core vesicle (DCV) exocytosis by binding to both phosphatidyl inositol 4,5-bisphosphate and DCVs in response to Ca 2+ increase [ 7 , 8 ]; it also interacts with the dopamine receptor [ 9 ]. A study of CAPS1-deficient mice suggested that CAPS1 is involved in catecholamine loading of DCVs in embryonic chromaffin cells [ 10 ]. On the other hand, CAPS2 is associated with secretory vesicles containing the neurotrophins BDNF and NT-3 in the parallel fiber terminals of cerebellar granule cells, and is involved in the release of BDNF and NT-3 [ 6 ]. CAPS2 is widely localized across various brain regions, and shows overlapping distribution patterns with BDNF in many areas [ 11 ]. Our recent

infinome is an experiment to study aging. Link your 23andMe account for personalized reports.

Gene: CAPS2 - calcyphosine 2 - (NCBI)

Images from Open Access Papers

Association Studies

Search Results from Open Access Papers