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Interactions between β2-syntrophin and a family of microtubule-associated serine/threonine kinases

Abstract

A screen for proteins that interact with β2-syntrophin led to the isolation of MAST205 (microtubule-associated serine/threonine kinase-205 kD) and a newly identified homologue, SAST (syntrophin-associated serine/threonine kinase). Binding studies showed that β2-syntrophin and MAST205/SAST associated via a PDZ–PDZ domain interaction. MAST205 colocalized with β2-syntrophin and utrophin at neuromuscular junctions. SAST colocalized with syntrophin in cerebral vasculature, spermatic acrosomes and neuronal processes. SAST and syntrophin were highly associated with purified microtubules and microtubule-associated proteins, whereas utrophin and dystrophin were only partially associated with microtubules. Our data suggest that MAST205 and SAST link the dystrophin/utrophin network with microtubule filaments via the syntrophins.

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Figure 1: β2-syntrophin interacts with MAST205 and SAST.
Figure 2: Expression of MAST205 and SAST in adult mouse tissues.
Figure 3: MAST205 localization in muscles of wild-type and mdx mice.
Figure 4: SAST localization in the brain and testes.
Figure 5: SAST and syntrophin in cultured neurons and in PSD preparations.
Figure 6: SAST, syntrophin, utrophin and dystrophin are associated with the microtubule network.

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Acknowledgements

We thank Lawrence Mathews for advice, discussions and plasmids and Tressia Hutchinson for technical assistance. We are also indebted to Stephen Elledge (Baylor College of Medicine) for providing plamids and yeast strains and to Stanley Froehner (University of North Carolina) and Glen Morris (MRIC Biochemistry Group, UK) for antibodies. Supported by grants from the National Institutes of Health (AR44533) and from the Muscular Dystrophy Association (USA) to J.S.C. Also supported by the U.M. Multipurpose Arthritis and Musculoskeletal Disease Center (NIHP60AR20557).

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Correspondence to Jeffrey S. Chamberlain.

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Lumeng, C., Phelps, S., Crawford, G. et al. Interactions between β2-syntrophin and a family of microtubule-associated serine/threonine kinases. Nat Neurosci 2, 611–617 (1999). https://doi.org/10.1038/10165

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