A γ-Aminobutyric Acid Transporter Driven by a Proton Pump is Present in Synaptic-Like Microvesicles of Pancreatic β Cells

A variety of peptide-secreting endocrine cells contain a population of recycling microvesicles that share several major membrane polypeptides with neuronal synaptic vesicles (SVs). The function of these synaptic-like microvesicles (SLMVs) remains to be elucidated. It was previously suggested that SLMVs of pancreatic β cells may store and secrete γ-aminobutyric acid (GABA). GABA, the major nonpeptide inhibitory neurotransmitter of the central nervous system, is stored in and secreted from SVs. GABA uptake into SVs is mediated by a transporter that is driven by a vacuolar proton ATPase. GABA is also present at high concentration in the endocrine pancreas where it is selectively localized in insulinsecreting β cells, the core cells of pancreatic islets. GABA is not present in peripheral islet cells (mantle cells), represented primarily by glucagon-secreting α cells. In this study, an immunoisolation procedure was used to purify SLMVs from cell lines derived from mouse β cells and α cells. SLMVs obtained from the β-cell line, but not those obtained from the α-cell line, displayed a GABA-transport activity dependent upon a proton electrochemical gradient generated by a vacuolar proton ATPase. These data support the hypotheses that (i) SLMVs have a secretory function similar to that of SVs and (ii) β-cell SLMVs are involved in the secretion of GABA, which in turn may have a paracrine function on mantle cells of the islet.