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Snap25基因中外显子5的古老复制对于复杂的神经元发育/功能是必需的。

An ancient duplication of exon 5 in the Snap25 gene is required for complex neuronal development/function.

作者信息

Johansson Jenny U, Ericsson Jesper, Janson Juliette, Beraki Simret, Stanić Davor, Mandic Slavena A, Wikström Martin A, Hökfelt Tomas, Ogren Sven Ove, Rozell Björn, Berggren Per-Olof, Bark Christina

机构信息

The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden.

出版信息

PLoS Genet. 2008 Nov;4(11):e1000278. doi: 10.1371/journal.pgen.1000278. Epub 2008 Nov 28.

DOI:10.1371/journal.pgen.1000278
PMID:19043548
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2581893/
Abstract

Alternative splicing is an evolutionary innovation to create functionally diverse proteins from a limited number of genes. SNAP-25 plays a central role in neuroexocytosis by bridging synaptic vesicles to the plasma membrane during regulated exocytosis. The SNAP-25 polypeptide is encoded by a single copy gene, but in higher vertebrates a duplication of exon 5 has resulted in two mutually exclusive splice variants, SNAP-25a and SNAP-25b. To address a potential physiological difference between the two SNAP-25 proteins, we generated gene targeted SNAP-25b deficient mouse mutants by replacing the SNAP-25b specific exon with a second SNAP-25a equivalent. Elimination of SNAP-25b expression resulted in developmental defects, spontaneous seizures, and impaired short-term synaptic plasticity. In adult mutants, morphological changes in hippocampus and drastically altered neuropeptide expression were accompanied by severe impairment of spatial learning. We conclude that the ancient exon duplication in the Snap25 gene provides additional SNAP-25-function required for complex neuronal processes in higher eukaryotes.

摘要

可变剪接是一种进化创新，可从有限数量的基因中产生功能多样的蛋白质。在调节性胞吐过程中，SNAP-25通过将突触小泡与质膜连接起来，在神经胞吐中发挥核心作用。SNAP-25多肽由单拷贝基因编码，但在高等脊椎动物中，外显子5的重复导致了两种相互排斥的剪接变体，即SNAP-25a和SNAP-25b。为了研究这两种SNAP-25蛋白之间潜在的生理差异，我们通过用第二个等效的SNAP-25a外显子替换SNAP-25b特异性外显子，生成了基因靶向的SNAP-25b缺陷小鼠突变体。SNAP-25b表达的消除导致发育缺陷、自发性癫痫发作和短期突触可塑性受损。在成年突变体中，海马体的形态变化以及神经肽表达的显著改变伴随着空间学习能力的严重受损。我们得出结论，Snap25基因中古老的外显子重复为高等真核生物复杂神经元过程提供了额外的SNAP-25功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbd/2581893/c8c3929aeb88/pgen.1000278.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbd/2581893/e582d91cee2f/pgen.1000278.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbd/2581893/f5f26c6a46e7/pgen.1000278.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbd/2581893/f5b0e148ed51/pgen.1000278.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbd/2581893/7029bd877cc4/pgen.1000278.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbd/2581893/c7f1ce7beb2e/pgen.1000278.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbd/2581893/c8c3929aeb88/pgen.1000278.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbd/2581893/e582d91cee2f/pgen.1000278.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbd/2581893/f5f26c6a46e7/pgen.1000278.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbd/2581893/f5b0e148ed51/pgen.1000278.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbd/2581893/7029bd877cc4/pgen.1000278.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbd/2581893/c7f1ce7beb2e/pgen.1000278.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbd/2581893/c8c3929aeb88/pgen.1000278.g006.jpg

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