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The recycling endosome and its role in neurological disorders
Authors:Li Xueyi  DiFiglia Marian
Affiliation:Laboratory of Cellular Neurobiology and Department of Neurology, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA.
Abstract:The recycling endosome (RE) is an organelle in the endocytic pathway where plasma membranes (proteins and lipids) internalized by endocytosis are processed back to the cell surface for reuse. Endocytic recycling is the primary way for the cell to maintain constituents of the plasma membrane (Griffiths et al., 1989), i.e., to maintain the abundance of receptors and transporters on cell surfaces. Membrane traffic through the RE is crucial for several key cellular processes including cytokinesis and cell migration. In polarized cells, including neurons, the RE is vital for the generation and maintenance of the polarity of the plasma membrane. Many RE dependent cargo molecules are known to be important for neuronal function and there is evidence that improper function of key proteins in RE-associated pathways may contribute to the pathogenesis of neurological disorders, including Huntington's disease. The function of the RE in neurons is poorly understood. Therefore, there is need to understand how membrane dynamics in RE-associated pathways are affected or participate in the development or progression of neurological diseases. This review summarizes advances in understanding endocytic recycling associated with the RE, challenges in elucidating molecular mechanisms underlying RE function, and evidence for RE dysfunction in neurological disorders.
Keywords:AD, Alzheimer's disease   AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid   APP, amyloid precursor protein   CHO, Chinese hamster ovary   EAAC1, excitatory amino acid carrier 1   EAAT3, excitatory amino acid transporter 3   EE, early endosome   EHD, Eps15 homology (EH) domain containing protein (EHD)   ER, endoplasmic reticulum   ES, embryonic stem   GAP, GTPase-activating protein   GDF, GDI-displacement factor   GEF, guanine nucleotide exchange factor   HD, Huntington's disease   HRP, horseradish peroxidase   Htt, huntingtin   LE, late endosome   α2-M, α2-microglobulin   MDCK, Madin–Darby canine kidney   PrP, prion protein   Rab11FIP, Rab11 family interacting protein   rabGDI, rabGDP dissociation inhibitor   RE, recycling endosome   SE, sorting endosome   SH3TC2, Src homology 3 domain and tetratricopeptide repeat 2   SNARE, soluble N-ethylmaleimide-sensitive factor attachment protein receptor   Tfn, transferrin   TfnR, transferrin receptor   TNFα, tumor necrosis factor α   tTGase, tissue transglutaminase   VAMP, vesicle-associated membrane protein
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