CLN3, at the crossroads of endocytic trafficking

NEUROSCIENCE LETTERS

卷:762

Article

Cotman, Susan L.¹  Lefrancois, Stephane^2,3,4 

[1] Massachusetts Gen Hosp, Mass Gen Res Inst, Dept Neurol, Ctr Genom Med, 185 Cambridge St, Boston, MA 02114 USA

[2] Inst Natl Rech Sci, Ctr Armand Frappier Sant prime Biotechnol, Laval, PQ H7V 1B7, Canada

[3] McGill Univ, Dept Anat & Cell Biol, Montreal, PQ H3A 0C7, Canada

[4] Univ Quebec Montreal UQAM, Ctr Excellence Rech Malad Orphelines Fdn Courtois, Montreal, PQ H2X 3Y7, Canada

关键词: CLN3;    Cytoskeleton;    Actin;    Ion channels;    Intracellular trafficking;    Endocytosis;    Autophagy;   

DOI  :  10.1016/j.neulet.2021.136117

来源: Elsevier

【 摘 要 】

The CLN3 gene was identified over two decades ago, but the primary function of the CLN3 protein remains unknown. Recessive inheritance of loss of function mutations in CLN3 are responsible for juvenile neuronal ceroid lipofuscinosis (Batten disease, or CLN3 disease), a fatal childhood onset neurodegenerative disease causing vision loss, seizures, progressive dementia, motor function loss and premature death. CLN3 is a multipass transmembrane protein that primarily localizes to endosomes and lysosomes. Defects in endocytosis, autophagy, and lysosomal function are common findings in CLN3-deficiency model systems. However, the molecular mechanisms underlying these defects have not yet been fully elucidated. In this mini-review, we will summarize the current understanding of the CLN3 protein interaction network and discuss how this knowledge is starting to delineate the molecular pathogenesis of CLN3 disease. Accumulating evidence strongly points towards CLN3 playing a role in regulation of the cytoskeleton and cytoskeletal associated proteins to tether cellular membranes, regulation of membrane complexes such as channels/transporters, and modulating the function of small GTPases to effectively mediate vesicular movement and membrane dynamics.

【 授权许可】

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