Editors' ChoiceChemotaxis

Gradient Amplification with Adenylyl Cyclase

Science's STKE  04 Mar 2003:
Vol. 2003, Issue 172, pp. tw90-TW90
DOI: 10.1126/stke.2003.172.tw90

Dictyostelium has proven a valuable model organism for understanding how cells sense and orient themselves in a gradients of chemotactic signals. Kriebel et al. add another piece to the puzzle with studies of mutant amoebae lacking the adenylyl cyclase ACA. The mutant cells were still able to respond to a gradient of the chemoattractant cAMP (adenosine 3′,5′-monophosphate), but they did not align themselves in the usual head-to-tail streams characteristic of wild-type cells. Visualization of fluorescently tagged ACA showed that although the ACA activator CRAC (cytosolic regulator of adenylyl cyclase) localizes to the front or leading edge of the cell, ACA molecules become concentrated at the rear end of migrating cells. ACA was also found in intracellular vesicles. CRAC was not necessary for localization of ACA, nor was PKA (cAMP-dependent protein kinase A). A constitutively active ACA mutant showed weaker localization to the back of the cell. In mixed cultures of wild-type cells and cells lacking ACA, the wild-type cells lined up in a head-to-tail fashion in streams, whereas cells lacking ACA failed to form streams or acted to terminate strings of streaming cells. The authors propose that in cells detecting a chemical gradient, ACA becomes asymmetrically distributed, perhaps by transport in intracellular vesicles. This would serve to amplify the polarized characteristics of the cell. High concentrations of cAMP produced at the rear of the cell by accumulated ACA may in turn cause attraction of cells behind and contribute to the alignment of cells in streams.

P. W. Kriebel, V. A. Barr, C. A. Parent, Adenylyl cyclase localization regulates streaming during chemotaxis. Cell 112, 549-560 (2003). [Online Journal]