the alstr？m syndrome protein, alms1, interacts with α-actinin and components of the endosome recycling pathwayalstr m综合症蛋白质、alms1与α-actinin和组件的内体回收途径.pdf

¨ The Alstrom Syndrome Protein, ALMS1, Interacts with a- Actinin and Components of the Endosome Recycling Pathway 1 1 1,2 3 3 4 Gayle B. Collin , Jan D. Marshall , Benjamin L. King , Gabriella Milan , Pietro Maffei , Daniel J. Jagger , ¨ 1 Jurgen K. Naggert * 1The Jackson Laboratory, Bar Harbor, Maine, United States of America, 2 Mount Desert Island Biological Laboratory, Salisbury Cove, Maine, United States of America, 3 Department of Medical and Surgical Sciences, University of Padua, Padua, Italy, 4 UCL Ear Institute, University College London, London, United Kingdom Abstract ¨ Alstrom syndrome (ALMS) is a progressive multi-systemic disorder characterized by cone-rod dystrophy, sensorineural hearing loss, childhood obesity, insulin resistance and cardiac, renal, and hepatic dysfunction. The gene responsible for ¨ Alstrom syndrome, ALMS1, is ubiquitously expressed and has multiple splice variants. The protein encoded by this gene has been implicated in ciliary function, cell cycle control, and intracellular transport. To gain better insight into the pathways through which ALMS1 functions, we carried out a yeast two hybrid (Y2H) screen in several mouse tissue libraries to identify ALMS1 interacting partners. The majority of proteins found to interact with the murine carboxy-terminal end (19/32) of ALMS1 were a-actinin isoforms. Interestingly, several of the identified ALMS1 interacting partners (a-actinin 1, a-actinin 4, myosin Vb, rad50 interacting 1 and huntingtin associated protein1A) have been previously associated with endosome recycling and/or centrosome function. We examined