Open AccessNovel calpain families and novel mechanisms for calpain regulation in Aplysia
Author(s) -
Margaret H. Hastings,
Katrina Gong,
Alexander Freibauer,
Caitlin Courchesne,
Xiaotang Fan,
Wayne S. Sossin
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0186646
Subject(s) - calpain , aplysia , proteases , biology , microbiology and biotechnology , calpastatin , alternative splicing , gene isoform , biochemistry , gene , neuroscience , enzyme
Calpains are a family of intracellular proteases defined by a conserved protease domain. In the marine mollusk Aplysia californica , calpains are important for the induction of long-term synaptic plasticity and memory, at least in part by cleaving protein kinase Cs (PKCs) into constitutively active kinases, termed protein kinase Ms (PKMs). We identify 14 genes encoding calpains in Aplysia using bioinformatics, including at least one member of each of the four major calpain families into which metazoan calpains are generally classified, as well as additional truncated and atypical calpains. Six classical calpains containing a penta-EF-hand (PEF) domain are present in Aplysia . Phylogenetic analysis determined that these six calpains come from three separate classical calpain families. One of the classical calpains in Aplysia , AplCCal1, has been implicated in plasticity. We identify three splice cassettes and an alternative transcriptional start site in AplCCal1. We characterize several of the possible isoforms of AplCCal1 in vitro , and demonstrate that AplCCal1 can cleave PKCs into PKMs in a calcium-dependent manner in vitro . We also find that AplCCal1 has a novel mechanism of auto-inactivation through N-terminal cleavage that is modulated through its alternative transcriptional start site.