The BAR domain protein Arfaptin-1 controls secretory granule biogenesis at the trans-Golgi network

Dev Cell. 2012 Oct 16;23(4):756-68. doi: 10.1016/j.devcel.2012.07.019. Epub 2012 Sep 13.


BAR domains can prevent membrane fission through their ability to shield necks of budding vesicles from fission-inducing factors. However, the physiological role of this inhibitory function and its regulation is unknown. Here we identify a checkpoint involving the BAR-domain-containing protein Arfaptin-1 that controls biogenesis of secretory granules at the trans-Golgi network (TGN). We demonstrate that protein kinase D (PKD) phosphorylates Arfaptin-1 at serine 132, which disrupts the ability of Arfaptin-1 to inhibit the activity of ADP ribosylation factor, an important component of the vesicle scission machinery. The physiological significance of this regulatory mechanism is evidenced by loss of glucose-stimulated insulin secretion due to granule scission defects in pancreatic β cells expressing nonphosphorylatable Arfaptin-1. Accordingly, depletion of Arfaptin-1 leads to the generation of small nonfunctional secretory granules. Hence, PKD-mediated Arfaptin-1 phosphorylation is necessary to ensure biogenesis of functional transport carriers at the TGN in regulated secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factors / antagonists & inhibitors
  • ADP-Ribosylation Factors / metabolism
  • Animals
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Phosphorylation
  • Protein Kinase C / metabolism
  • Protein Structure, Tertiary
  • Rats
  • Secretory Vesicles / metabolism*
  • Serine / metabolism
  • trans-Golgi Network / metabolism*


  • Carrier Proteins
  • arfaptin 1, rat
  • Serine
  • protein kinase D
  • Protein Kinase C
  • ADP-Ribosylation Factors