Editors' ChoiceCell Biology

Taking Turns Sending and Receiving

Science Signaling  24 Nov 2009:
Vol. 2, Issue 98, pp. ec379
DOI: 10.1126/scisignal.298ec379

Cellular communication occurs between cells that are typically defined as the signal-sending cell and the signal-receiving cell. Sometimes self-stimulation of the signal-sending cell is desirable, such as in the clonal expansion of immune cells. Other times, it is necessary for the two cells to be distinguishable from each other. This can be achieved by having cells that are developmentally or genetically distinct interact. Sometimes, however, it is necessary for developmentally and genetically identical cells to communicate and respond to the same signals, yet avoid self-stimulation. Fleissner et al. hypothesized that in the latter situation the cells would alternate between serving as the signal-sending cell and the signal-receiving cell. To test this hypothesis, they investigated the chemotropic interactions of Neurospora crassi “germlings” (germinating asexual spores) that are attracted to each other to fuse and form hyphae called conidial anastomosis tubes (CATs). They monitored the localization of two proteins (the mitogen-activated protein kinase MAK-2 and the WW domain protein SO) essential for chemotropism and CAT formation and found that, when two cells were interacting, MAK-2 and SO were recruited to the tips of the interacting cells in an oscillating manner. Furthermore, when MAK-2 was abundant at the tip, SO was not, and vice versa, so that the partner cells appeared to oscillate between states, presumably one sending a signal while the other was receiving, and then switching. Introduction of an inhibitable form of MAK-2 prevented chemotropism and CAT formation when the inhibitor was added. To assess the importance of MAK-2 activity in the recruitment of MAK-2 in the partner cell, cells wild-type for MAK-2 were mixed with cells expressing the inhibitable MAK-2 variant and allowed to interact, and then the inhibitor was added. Wild-type MAK-2 failed to localize to the cell tip when the partner cell’s MAK-2 activity was inhibited. Furthermore, addition of the inhibitor to MAK-2 inhibitor variant cells interacting with wild-type SO cells resulted in the stabilization of SO at the partner cell tip. Thus, the kinase activity of MAK-2 has a non–cell autonomous function in MAK-2 recruitment to and SO dispersal from the partner cell tip.

A. Fleissner, A. C. Leeder, M. G. Roca, N. D. Read, N. L. Glass, Oscillatory recruitment of signaling proteins to cell tips promotes coordinated behavior during cell fusion. Proc. Natl. Acad. Sci. U.S.A. 106, 19387–19392 (2009). [Abstract] [Full Text]