Research article

Fak56 functions downstream of integrin alphaPS3betanu and suppresses MAPK activation in neuromuscular junction growth

Pei-I Tsai^1,2 , Hsiu-Hua Kao³ , Caroline Grabbe⁴ , Yu-Tao Lee³ , Aurnab Ghose^5,7 , Tzu-Ting Lai¹ , Kuan-Po Peng¹ , David Van Vactor⁵ , Ruth H Palmer⁴ , Ruey-Hwa Chen^2,6 , Shih-Rung Yeh³ and Cheng-Ting Chien^1,2

¹  Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan

²  Institute of Molecular Medicine, National Taiwan University, Taipei 106, Taiwan

³  Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 300, Taiwan

⁴  Umeå Center for Molecular Pathogenesis, Umeå University, Umeå, S-901 87, Sweden

⁵  Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA

⁶  Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan

⁷  Indian Institute of Science Education and Research, 900, NCL Innovation Park, Homi Bhabha Road, Pune 411008, India

author email corresponding author email

Neural Development 2008, 3:26doi:10.1186/1749-8104-3-26

Published:	16 October 2008

Abstract

Background

Focal adhesion kinase (FAK) functions in cell migration and signaling through activation of the mitogen-activated protein kinase (MAPK) signaling cascade. Neuronal function of FAK has been suggested to control axonal branching; however, the underlying mechanism in this process is not clear.

Results

We have generated mutants for the Drosophila FAK gene, Fak56. Null Fak56 mutants display overgrowth of larval neuromuscular junctions (NMJs). Localization of phospho-FAK and rescue experiments suggest that Fak56 is required in presynapses to restrict NMJ growth. Genetic analyses imply that FAK mediates the signaling pathway of the integrin αPS3βν heterodimer and functions redundantly with Src. At NMJs, Fak56 downregulates ERK activity, as shown by diphospho-ERK accumulation in Fak56 mutants, and suppression of Fak56 mutant NMJ phenotypes by reducing ERK activity.

Conclusion

We conclude that Fak56 is required to restrict NMJ growth during NMJ development. Fak56 mediates an extracellular signal through the integrin receptor. Unlike its conventional role in activating MAPK/ERK, Fak56 suppresses ERK activation in this process. These results suggest that Fak56 mediates a specific neuronal signaling pathway distinct from that in other cellular processes.