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The role of the retromer complex in aging-related neurodegeneration: a molecular and genomic review

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An Erratum to this article was published on 06 March 2015

Abstract

The retromer coat complex is a vital component of the intracellular trafficking mechanism sorting cargo from the endosomes to the trans-Golgi network or to the cell surface. In recent years, genes encoding components of the retromer coat complex and members of the vacuolar protein sorting 10 (Vps10) family of receptors, which play pleiotropic functions in protein trafficking and intracellular/intercellular signaling in neuronal and non-neuronal cells and are primary cargos of the retromer complex, have been implicated as genetic risk factors for sporadic and autosomal dominant forms of several neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and frontotemporal lobar degeneration. In addition to their functions in protein trafficking, the members of the Vps10 receptor family (sortilin, SorL1, SorCS1, SorCS2, and SorCS3) modulate neurotrophic signaling pathways. Both sortilin and SorCS2 act as cell surface receptors to mediate acute responses to proneurotrophins. In addition, sortilin can modulate the intracellular response to brain-derived neurotrophic factor (BDNF) by direct control of BDNF levels and regulating anterograde trafficking of Trk receptors to the synapse. This review article summarizes the emerging data from this rapidly growing field of intracellular trafficking signaling in the pathogenesis of neurodegeneration.

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Acknowledgments

Dr. Reitz was supported by a Paul B. Beeson Career Development Award (K23AG034550).

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  1. The Department of Neurology, The Department of Epidemiology, The Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, The Gertrude H. Sergievsky Center, Columbia University, 630 West 168th Street, New York, NY, 10032, USA

    Christiane Reitz

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Correspondence to Christiane Reitz.

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Communicated by S. Hohmann.

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Reitz, C. The role of the retromer complex in aging-related neurodegeneration: a molecular and genomic review. Mol Genet Genomics 290, 413–427 (2015). https://doi.org/10.1007/s00438-014-0939-9

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