Definition of Munc13-homology-domains and characterization of a novel ubiquitously expressed Munc13 isoform

Munc13 proteins constitute a family of three highly homologous molecules (M unc13-1, Munc13-2 and Munc13-3). With the exception of a ubiquitously expre ssed Munc13-2 splice variant, Munc13 proteins are brain-specific. Munc13-1 has a central priming function in synaptic vesicle exocytosis from glutamat ergic 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 ar e 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 characteri zed a novel, ubiquitously expressed, rat protein (Munc13-4) that belongs to a subfamily of Munc13-like molecules, in which the typical Munc13-like dom ain structure is conserved. Munc13-4 is predominantly expressed in lung whe re it is localized to goblet cells of the bronchial epithelium and to alveo lar 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 identific ation of Munc13-like proteins, that would otherwise have remained undetecte d.