HS1-Associated Protein X-1 Interacts with Membrane-Bound IgE: Impact on Receptor-Mediated Internalization

Abstract

Engagement of the BCR triggers signals that control affinity maturation, memory induction, differentiation, and various other physiological processes in B cells. In previous work, we showed that truncation of the cytoplasmic tail of membrane-bound Ig (mIg)E in vivo resulted in lower serum IgE levels, decreased numbers of IgE-secreting plasma cells, and the abrogation of specific secondary responses correlating with a defect in the selection of high-affinity Abs during the germinal center reaction. We concluded that the Ag receptor is necessary at all times during Ab responses not only for the maturation process, but also for the expansion of Ag-specific B cells. Based on these results, we asked whether the cytoplasmic tail of mIgE, or specific proteins binding the cytoplasmic tail in vivo commit a signal transduction accompanying the B cell along its differentiation process. In this study, we present the identification of HS1-associated protein X-1 as a novel protein interacting with the cytoplasmic tail of mIgE. ELISA, surface plasmon resonance analysis, and coimmunoprecipitation experiments confirmed the specific interaction in vitro. In functional assays, we clearly showed that HS1-associated protein X-1 expression levels influence the efficiency of BCR-mediated Ag internalization.

Hepatitis C Virus Core Protein and Cellular Protein HAX-1 Promote 5-Fluorouracil-Mediated Hepatocyte Growth Inhibition

“…Upon interaction with other cellular proteins, its subcellular localization is redistributed, and this may play an important role in modulating different biological activities (19). Vafiadaki et al (38) reported that an association of HAX-1 with phospholamban, a key regulator of contractibility in the heart, leads to redistribution and colocalization of HAX-1 with phospholamban at the endoplasmic reticulum.…”

“…The biological function of HAX-1 was primarily divided into three categories: (i) association with viral proteins for involvement in apoptotic regulation processes, (ii) involvement in cell motility processes, and (iii) acting as a cytoplasmic retention factor. HAX-1 mRNA is expressed ubiquitously in different tissues, including liver (17,19). Several studies have shown that Hax-1 expression is upregulated in different types of tumors (7,14,17,41,42).…”

HAX1 deficiency: Impact on lymphopoiesis and B‐cell development

“…Previously, we described HAX1 as interaction partner of membrane bound IgE (mIgE) [24]. From that point of view, it would have been of most interest to analyse IgE responses on a Hax1-deficient background.…”

AID-induced remodeling of immunoglobulin genes and B cell fate

“…HS1-associated protein X-1 (HAX-1) notably seems to be associated with the IgE specific YANIL motif (where Y is a potentially phosphorylated tyrosine) of the intra-cellular tail and may influence BCR mediated Ag-internalization and cognate Ag-presentation to T cells [61]. Hematopoietic progenitor kinase 1 (HPK1) was also shown to interact with mIgE and mIgG (but not mIgM) tails and could differentially affect signaling from these receptors [62].…”