title: Definition of Munc13-homology-domains and characterization of a novel ubiquitously expressed Munc13 isoform.
abstract: Munc13 proteins constitute a family of three highly homologous molecules (Munc13-1, Munc13-2 and Munc13-3). With the exception of a ubiquitously expressed Munc13-2 splice variant, Munc13 proteins are brain-specific. Munc13-1 has a central priming function in synaptic vesicle exocytosis from glutamatergic synapses. In order to identify Munc13-like proteins that may regulate secretory processes in non-glutamatergic neurons or non-neuronal cells, we developed protein profiles for two Munc13-homology-domains (MHDs). MHDs are present in a wide variety of proteins, some of which have previously been implicated in membrane trafficking reactions. Taking advantage of partial sequences in the human expressed sequence tag (EST) database, we characterized a novel, ubiquitously expressed, rat protein (Munc13-4) that belongs to a subfamily of Munc13-like molecules, in which the typical Munc13-like domain structure is conserved. Munc13-4 is predominantly expressed in lung where it is localized to goblet cells of the bronchial epithelium and to alveolar type II cells, both of which are cell types with secretory function. In the present study we identify a group of novel proteins, some of which may function in a Munc13-like manner to regulate membrane trafficking. The MHD profiles described in the present study are useful tools for the identification of Munc13-like proteins, that would otherwise have remained undetected.
authors.affiliation: Max-Planck-Institut für experimentelle Medizin, AG Molekulare Neurobiologie, Hermann-Rein-Str. 3, D-37075 Göttingen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Koch
authors.forename: K
authors.initials: K
authors.lastname: Hofmann
authors.forename: N
authors.initials: N
authors.lastname: Brose
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D003001:Cloning, Molecular; D020224:Expressed Sequence Tags; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016366:Open Reading Frames; D010802:Phylogeny; D014176:Protein Biosynthesis; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
chemical_list: D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D011506:Proteins; D012333:RNA, Messenger; C485548:UNC13B protein, human; C103912:Unc13a protein, rat; C117991:Unc13b protein, rat; C117992:Unc13c protein, rat; C430713:Unc13d protein, rat