Endoplasmic Reticulum Membrane-sorting Protein of Lymphocytes (BAP31) Is Highly Expressed in Neurons and Discrete Endocrine Cells

Abstract

S U M M A R YBAP31 is a transmembrane protein that associates with nascent membrane proteins in transit between endoplasmic reticulum (ER) and cis -Golgi. Its C-terminal dilysine (KKEE) motif, mediating return to the ER, is consistent with a role in early sorting of membrane proteins. An initiator caspase-binding site in the C-terminal domain of BAP31 is implicated in cytoplasmic membrane fragmentation events of apoptosis. Although BAP31 RNA is ubiquitous, the protein's anatomic localization has not been determined. To gain further insight into its possible functions, we localized BAP31 in primate tissues using monoclonal antibodies. Immunoreactivity was prominent in T-and B-lymphocytes in blood and in thymus, in cerebellar Purkinje neuron bodies and dendrites, in gonadotrophs of the anterior pituitary, ovarian thecal and follicular cells, active but not quiescent thyroid epithelium, adrenal cortex more than medulla, and proximal more than distal renal tubules. Blood vessels and skeletal muscle were nonreactive. The anatomic distribution of BAP31 and the nature of proteins identified thus far as its cargo exiting the ER, suggest an interaction with proteins assembling in macromolecular complexes en route to selected sites of exocytotic and signaling activities. Apoptotic associations in mature tissues could be physiological (lymphocytes, endocrine cells) or pathological (Purkinje neurons, renal tubules).

Association of BAP31 with CD11b/CD18

“…It has a cytoplasmic C terminus containing ␣-helical domains and a terminal dilysine ER-homing motif (26). Although cloning of human and murine cDNA showed that BAP31 is ubiquitously expressed in all tissues (26), BAP31 protein expression seems restricted to a minority of cells in tissues (35). In the present study, we have demonstrated the presence of BAP31 in human intestinal epithelial cells and PMN.…”

“…Previous studies on BAP31 have suggested that BAP31 is a component of the rough ER and ER-derived trafficking vesicles. It mainly localizes within ERlike structures and has been proposed to participate in regulating the export of selected membrane proteins from the ER to the Golgi apparatus (28,29,35,50). The localization pattern of BAP31 observed in human colonic epithelial cells would argue that BAP31 might also be involved in protein sorting or vesicle transport to cell basolateral surfaces.…”

“…This may represent the protein-sorting nature of BAP31. If BAP31 is responsible for protein transport between certain organelles (28,29,35), it would be expected to associate and dissociate with the proteins along the sorting pathway. Indeed, our subcellular fractionation studies suggest that BAP31 and CD11b/CD18 colocalize in secondary granules but not in other CD11b/CD18-containing granules such as tertiary granules.…”

Bifunctional apoptosis inhibitor (BAR) protects neurons from diverse cell death pathways

“…22 Interestingly, Bap31 expression is highest in neurons, lymphocytes, and endocrine cells. 31 Future investigations will reveal to what extent the interactions of these variant DED-containing proteins are relevant for BARmediated neuroprotection.…”

BAP31 is frequently overexpressed in patients with primary colorectal cancer and correlates with better prognosis

“…Some studies showed that overexpression of BAP31 increases the cell surface level of class I major histocompatibility complex (MHC) molecules [19]. BAP31 is very important in general cell processes including early secretory pathway trafficking of proteins and regulating the export of selected membrane proteins to the Golgi apparatus [18,20]. Additionally, as a mediator of apoptosis, full-length BAP31 acts as an inhibitor of apoptosis.…”