First published online March 8, 2006
Journal of Cell Science 119, 602e (2006)
© The Company of Biologists Limited
Setting a Crac-king pace
Eukaryotic cells sense chemical gradients during a variety of physiological processes and then move up or down the gradients by extending pseudopods. The molecular mechanisms involved in such chemotaxis are evolutionarily conserved and have been studied extensively in Dictyostelium. Pleckstrin homology (PH)-domain proteins bind to phosphatidylinositol 3,4,5-triphosphates [PtdIns(3,4,5)P3] at the leading edge of chemotaxing Dictyostelium cells to regulate pseudopod formation. Now, Masahiro Ueda and co-workers reveal that the steady-state localization of the PH-domain protein Crac at the leading edge pseudopod is maintained by rapid exchange of individual molecules (see p. 1071). The authors track single Crac-GFP molecules and report that most bind very transiently to PtdIns(3,4,5)P3 at the front of migrating cells; a few bind more stably to adenyl cyclase A (ACA)-dependent sites at the rear of the cells, where they might regulate ACA activity. The authors propose that the dynamic binding behaviour of PH-domain proteins allows Dictyostelium to reorientate rapidly in response to directional changes of chemoattractant and suggest that other chemotactic signalling components may exhibit dynamic behaviour similar to that of Crac.
Related articles in JCS:
- Single-molecule analysis of chemoattractant-stimulated membrane recruitment of a PH-domain-containing protein
- Satomi Matsuoka, Miho Iijima, Tomonobu M. Watanabe, Hidekazu Kuwayama, Toshio Yanagida, Peter N. Devreotes, and Masahiro Ueda
JCS 2006 119: 1071-1079.
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