Glycolipid-Rich Membrane Microdomains in Lacrimal Acinar Cell Endomembrane Compartments

Abstract

Extensive molecular trafficking exists between the basal-lateral plasma membrane (blm) and endomembrane compartments of lacrimal gland acinar cells. Proteins normally must be segregated consistently between the lacrimal acinar cell’s apical secretory pathway, lysosomal pathway, and basal-lateral membrane recycling pathway. A recent analytical subcellular fractionation study (Yang et al., 1999b) showed that significant changes in the distributions of a variety of endomembrane proteins occur when lacrimal acinar cells are stimulated with 10 µM carbachol for 20 min. In that study, the amount of β-hexosaminidase, typically a lysosomal enzyme, but also a secretory enzyme in lacrimal acinar cells, increased in isolated low-density trans-Golgi network (ld-tgns) believed to represent domains of the trans-Golgi network that mediate traffic to the basal-lateral membrane. This increase was accompanied by net redistributions of protein into the ld-tgns and blm of proteins from other endomembrane compartments. These included galactosyltransferase from the Golgi complex, Rab6 from domains of the high-density trans-Golgi network (hd-tgns) that are believed to mediate traffic both to secretory vesicles and pre-lysosomes (preLys), and immature forms of cathepsin B from the hd-tgns and preLys. We have proposed that such alterations of protein segregation and targeting in the endomembrane traffic might overwhelm peripheral tolerance mechanisms and provoke local autoimmune responses (Mircheff et al., 1996, Mircheff et al., this volume).