Syntaxin-4 is implicated in the secretion of antibodies by human plasma cells

J Leukoc Biol. 2014 Feb;95(2):305-12. doi: 10.1189/jlb.0113031. Epub 2013 Oct 21.

Abstract

PCs are responsible for the production and secretion of antibodies, the effector molecules of the humoral immune response. The molecular mechanisms responsible for vesicle docking and secretion implicated in the antibody-secretion process are not well-known, as they have not been studied, but it is known that SNARE proteins are responsible for many membrane-fusion processes in the cell. We show here that freshly isolated human colon LP-PCs and T-PCs from MM-PC patients and the U266 cell line, as a model for PC secretion, contain a set of these proteins. SNAP23, STX3, and STX4 were localized mainly in the plasma membrane of PCs, and interactions of SNAP23 with STX3 and with STX4 were proven by IP. Interaction between SNAP23 and STX4 was also confirmed in situ. With the use of siRNA, as well as shRNA, the functional role of SNAP23, STX3, and STX4 in antibody secretion was also examined. The findings demonstrate that in addition to SNAP23, STX4 is implicated in the antibody secretion by a myeloma cell line and by normal human colon LP-PCs.

Keywords: RNAi protein knockdown; SNARE; immunoglobulin exocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / metabolism*
  • Cell Line
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cell Separation
  • Doxycycline / pharmacology
  • Humans
  • Immunoglobulin A / biosynthesis
  • Immunoglobulin E / metabolism
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology
  • Plasma Cells / drug effects
  • Plasma Cells / metabolism*
  • Protein Binding / drug effects
  • Protein Transport / drug effects
  • Qa-SNARE Proteins / metabolism*
  • Qb-SNARE Proteins / metabolism
  • Qc-SNARE Proteins / metabolism
  • RNA, Small Interfering / metabolism
  • Subcellular Fractions / drug effects
  • Subcellular Fractions / metabolism

Substances

  • Antibodies
  • Immunoglobulin A
  • Qa-SNARE Proteins
  • Qb-SNARE Proteins
  • Qc-SNARE Proteins
  • RNA, Small Interfering
  • SNAP23 protein, human
  • syntaxin 4, human
  • Immunoglobulin E
  • Doxycycline