Inositol pyrophosphates regulate endocytic trafficking

doi:10.1073/pnas.212527899

Inositol pyrophosphates regulate endocytic trafficking

Departments of ^*Neuroscience, ^§Pharmacology and Molecular Sciences, and ^¶Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205; and ^‡Integrated Imaging Center, ^†Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218

Contributed by Solomon H. Snyder

Abstract

The high energy potential and rapid turnover of the recently discovered inositol pyrophosphates, such as diphosphoinositol-pentakisphosphate and bis-diphosphoinositol-tetrakisphosphate, suggest a dynamic cellular role, but no specific functions have yet been established. Using several yeast mutants with defects in inositol phosphate metabolism, we identify dramatic membrane defects selectively associated with deficient formation of inositol pyrophosphates. We show that this phenotype reflects specific abnormalities in endocytic pathways and not other components of membrane trafficking. Thus, inositol pyrophosphates are major regulators of endocytosis.

Footnotes

↵ ∥ To whom correspondence should be addressed. E-mail: ssnyder{at}bs.jhmi.edu.
Abbreviations:
1. IP₆, inositol hexakisphosphate
2. IP6K, IP₆ kinase
3. IP₇, diphosphoinositol-pentakisphosphate
4. IP₈, bis-diphosphoinositol-tetrakisphosphate
5. IPMK, inositol phosphate multikinase