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Session II : Receptor signaling and G proteins Poster II, 52
AF6 negatively regulates Rap1-induced cell adhesion
Zhongchun Zhang, Holger Rehmann, Leo S. Price, Jurgen Riedl, and Johannes L. Bos
From the Department of Physiological Chemistry and Centre of Biomedical Genetics,
University Medical Centre Utrecht, The Netherlands.
Address correspondence to Johannes L. Bos, Department of Physiological Chemistry
and Centre of Biomedical Genetics, University Medical Centre Utrecht, Universiteitsweg
100, 3584 CG Utrecht, The Netherlands. Tel. +31302538988; Fax. +31302539035 E-mail:
J.L.Bos@med.uu.nl
Small GTPases of the Ras family are molecular switches, whose functions are guiding
extracellular signals towards cellular responses. Rap, one of the most extensively-studied
members of the family, regulates cell proliferation, cell differentiation, cell death, and most
notable cell-matrix and cell-cell adhesion.
AF6 is involved in the connection of membrane-associated proteins to the actin cytoskeleton.
It binds to Ras-like small GTPases and is suggested to be an effector of both Ras and Rap.
In the absence of an immune challenge, T cells circulate the body in a non-adhesive state.
The maintenance of this non-adhesive condition prevents inappropriate immune responses
from occurring. An increase in Rap activation is sufficient to rapidly upregulate T cell
adhesiveness, demonstrating that Rap signaling must be tightly controlled in unstimulated T
cells.
In this study, we show that knockdown of AF6 in T lymphocyte by RNAi enhances Rap1induced
integrin-mediated cell adhesion, whereas overexpression of AF6 has the opposite
effect. We conclude that AF6 is a negative regulator of Rap-induced cell adhesion. In
addition, our results suggest that endogenous AF6 may function to buffer GTP-Rap in resting
cells, maintaining it in a non-productive complex. Therefore, loss of AF6 function may result
in immunological disorders.
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