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The Role of Retromer in Neurodegenerative Disease

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Intracellular Traffic and Neurodegenerative Disorders

Part of the book series: Research and Perspectives in Alzheimer's Disease ((ALZHEIMER))

Abstract

Bi-directional membrane traffic between the Golgi and endosomes plays a vital role in the biogenesis of lysosomes and the localisation of many membrane proteins with diverse physiological functions. The receptors that mediate sorting of lysosomal hydrolases at the Golgi traffic rapidly between the Golgi and endosomes to deliver newly synthesised hydrolases to a pre-lysosomal endosome before returning to the Golgi to repeat the process. The mislocalisation of endosomal and/or lysosomal proteins due to aberrant protein sorting can give rise to a range of pathologies, and there are emerging strands of evidence that defects in the endosome-to-Golgi retrieval pathway contribute significantly to neurodegenerative diseases such as Alzheimer's disease. The retromer complex that is conserved from yeast to humans plays a major role in endosomal protein sorting and is required for endosome-to-Golgi retrieval. In this review we will discuss the identification, assembly, membrane association and function of the retromer complex and will describe recent evidence linking retromer function with neurodegenerative disease.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Cambridge Institute for Medical Research, Wellcome Trust & MRC Building, Addenbrookes Hospital, Hills Road, Cambridge, CB2 2XY, UK

    Claire F. Skinner & Matthew N.J. Seaman

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  1. Claire F. Skinner
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  2. Matthew N.J. Seaman
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Editors and Affiliations

  1. Department of Laboratory Medicine and Pathobiology, University of Toronto, Tranz Neuroscience Bldg., Toronto, ON, M5S 3H2, Canada

    Peter H. St. George-Hyslop

  2. Department of Neurology, Standford University School of Medicine, Standford, CA, 94305-5316, USA

    William C. C. Mobley

  3. Fondation IPSEN Pour la Recherche Thérapeutique, 65, quai Georges Gorse, Boulogne Billancourt, 92650, Cedex - France

    Yves Christen

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© 2009 Springer-Verlag Berlin Heidelberg

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Skinner, C.F., Seaman, M.N. (2009). The Role of Retromer in Neurodegenerative Disease. In: George-Hyslop, P.H.S., Mobley, W.C., Christen, Y. (eds) Intracellular Traffic and Neurodegenerative Disorders. Research and Perspectives in Alzheimer's Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-87941-1_10

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