Role BAP31 complex at the endoplasmic reticulum in normal cell physiology and apoptosis

The endoplasmic reticulum (ER) plays a vital role in synthesis, folding and sorting of newly synthesized secretory cargo proteins. Quality control mechanism in the ER is a key regulator of this process, which separates correctly folded proteins from immature or misfolded secretory proteins, and ultimately retains and disposes the latter before they can exit the ER. Numerous diseases have been associated with defects in the regulation of the egress of the nascent membrane proteins out of ER to the cell surface. BAP31, a polytopic integral membrane protein at the ER, has been implicated as a putative quality control factor and/or cargo protein in regulating the export of specific sets of nascent membrane proteins. Here, I demonstrate BAP31 to be an important player in regulating and maintaining functional integrity of the cell surface. Both truncated (p20BAP31) and deletion (BAP31-null) mutants of BAP31 significantly abrogated expression of tetraspanins at the cell surface, and thus integrin-mediated cell adhesion and survival due to BAP31 effects on tetraspanin transport from the ER. Consistent with its role as a chaperone or cargo receptor, BAP31 was found to interact with Sec61beta and TRAM, components of the nascent protein translocation machinery and to form an important part of the ribosome-translocon complexes at the ER. In addition to its predicted role in quality control mechanism in the ER, BAP31, a BCL-2 associated protein, is recognized as an important regulator of apoptosis, an essential physiological mechanism of cell suicide in development and homeostasis in all multicellular organisms. Here, I characterized SPIKE, a new proposed pro-apoptotic BCL-2 protein and interacting partner of BAP31. SPIKE is a novel and untypical pro-apoptotic BH3 only protein capable of inducing apoptosis without binding to anti-apoptotic BCL-2 partners and endogenous BAP31, whose role in specific apoptotic pathway remains to be elucidated. Thus, BAP31 plays important, but distinct roles in both normal cell physiology and apoptosis