Integration of Golgi trafficking and growth factor signaling by the lipid phosphatase SAC1

Anastasia Blagoveshchenskaya, Ying Cheong Fei, Holger M. Rohde, Greta Glover, Andreas Knödler, Teresa Nicolson, Guido Boehmelt, Peter Mayinger

Research output: Contribution to journalArticlepeer-review

126 Scopus citations


When a growing cell expands, lipids and proteins must be delivered to its periphery. Although this phenomenon has been observed for decades, it remains unknown how the secretory pathway responds to growth signaling. We demonstrate that control of Golgi phosphatidylinositol-4-phosphate (PI(4)P) is required for growth-dependent secretion. The phosphoinositide phosphatase SAC1 accumulates at the Golgi in quiescent cells and down-regulates anterograde trafficking by depleting Golgi PI(4)P. Golgi localization requires oligomerization of SAC1 and recruitment of the coat protein (COP) II complex. When quiescent cells are stimulated by mitogens, SAC1 rapidly shuttles back to the endoplasmic reticulum (ER), thus releasing the brake on Golgi secretion. The p38 mitogen-activated kinase (MAPK) pathway induces dissociation of SAC1 oligomers after mitogen stimulation, which triggers COP-I-mediated retrieval of SAC1 to the ER. Inhibition of p38 MAPK abolishes growth factor-induced Golgi-to-ER shuttling of SAC1 and slows secretion. These results suggest direct roles for p38 MAPK and SAC1 in transmitting growth signals to the secretory machinery.

Original languageEnglish (US)
Pages (from-to)803-812
Number of pages10
JournalJournal of Cell Biology
Issue number4
StatePublished - Feb 25 2008

ASJC Scopus subject areas

  • Cell Biology


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