Open Close
Reference
Citation
Moreau, K., Fleming, A., Imarisio, S., Lopez Ramirez, A., Mercer, J.L., Jimenez-Sanchez, M., Bento, C.F., Puri, C., Zavodszky, E., Siddiqi, F., Lavau, C.P., Betton, M., O'Kane, C.J., Wechsler, D.S., Rubinsztein, D.C. (2014). PICALM modulates autophagy activity and tau accumulation.  Nat. Commun. 5(): 4998.
FlyBase ID
FBrf0235184
Publication Type
Research paper
Abstract

Genome-wide association studies have identified several loci associated with Alzheimer's disease (AD), including proteins involved in endocytic trafficking such as PICALM/CALM (phosphatidylinositol binding clathrin assembly protein). It is unclear how these loci may contribute to AD pathology. Here we show that CALM modulates autophagy and alters clearance of tau, a protein which is a known autophagy substrate and which is causatively linked to AD, both in vitro and in vivo. Furthermore, altered CALM expression exacerbates tau-mediated toxicity in zebrafish transgenic models. CALM influences autophagy by regulating the endocytosis of SNAREs, such as VAMP2, VAMP3 and VAMP8, which have diverse effects on different stages of the autophagy pathway, from autophagosome formation to autophagosome degradation. This study suggests that the AD genetic risk factor CALM modulates autophagy, and this may affect disease in a number of ways including modulation of tau turnover.

PubMed ID
PubMed Central ID
PMC4199285 (PMC) (EuropePMC)
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Nat. Commun.
    Title
    Nature communications
    ISBN/ISSN
    2041-1723
    Data From Reference
    Alleles (11)
    Genes (3)
    Human Disease Models (1)
    Natural transposons (1)
    Insertions (4)
    Experimental Tools (1)
    Transgenic Constructs (8)