Regulated resurfacing of a somatostatin receptor storage compartment fine-tunes pituitary secretion

J Cell Biol. 2020 Jan 6;219(1):e201904054. doi: 10.1083/jcb.201904054.


The surfacing of the glucose transporter GLUT4 driven by insulin receptor activation provides the prototypic example of a homeostasis response dependent on mobilization of an intracellular storage compartment. Here, we generalize this concept to a G protein-coupled receptor, somatostatin receptor subtype 2 (SSTR2), in pituitary cells. Following internalization in corticotropes, SSTR2 moves to a juxtanuclear syntaxin-6-positive compartment, where it remains until the corticotropes are stimulated with corticotropin releasing factor (CRF), whereupon SSTR2 exits the compartment on syntaxin-6-positive vesicular/tubular carriers that depend on Rab10 for their fusion with the plasma membrane. As SSTR2 activation antagonizes CRF-mediated hormone release, this storage/resurfacing mechanism may allow for a physiological homeostatic feedback system. In fact, we find that SSTR2 moves from an intracellular compartment to the cell surface in pituitary gland somatotropes, concomitant with increasing levels of serum growth hormone (GH) during natural GH cycles. Our data thus provide a mechanism by which signaling-mediated plasma membrane resurfacing of SSTR2 can fine-tune pituitary hormone release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Corticotrophs / metabolism*
  • Corticotropin-Releasing Hormone
  • Human Growth Hormone / metabolism*
  • Humans
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pituitary Gland / cytology
  • Pituitary Gland / metabolism*
  • Qa-SNARE Proteins / genetics
  • Qa-SNARE Proteins / metabolism*
  • Receptors, Somatostatin / genetics
  • Receptors, Somatostatin / metabolism*
  • Signal Transduction
  • rab GTP-Binding Proteins / physiology*


  • Qa-SNARE Proteins
  • Receptors, Somatostatin
  • SSTR2 protein, human
  • STX6 protein, human
  • Human Growth Hormone
  • Corticotropin-Releasing Hormone
  • Rab10 protein, mouse
  • rab GTP-Binding Proteins

Grant support