relationship between cip2a and chaperone mediated autophagy

T1 - Molecular determinants of the crosstalk between endosomal microautophagy and chaperone-mediated autophagy Collectively, these results show a coordinated function of eMI with CMA, identify the interchangeable subproteome degraded by these pathways, and start to elucidate the molecular mechanisms that facilitate the switch between them.', Association and dynamics of Bag6 at the late endosome membrane change during starvation, a stressor that, contrary to other autophagic pathways, causes a decline in eMI activity. In this work, we show the existence of a compensatory relationship between CMA and eMI and identify a role for the chaperone protein Bag6 in triage and internalization of eMI substrates into late endosomes. These autophagic processes share as a first step the recognition of the same five-amino-acid motif in substrate proteins by the Hsc70 chaperone, raising the possibility of coordinated activity of both pathways. Collectively, these results show a coordinated function of eMI with CMA, identify the interchangeable subproteome degraded by these pathways, and start to elucidate the molecular mechanisms that facilitate the switch between them.Ībstract = 'Chaperone-mediated autophagy (CMA) and endosomal microautophagy (eMI) are pathways for selective degradation of cytosolic proteins in lysosomes and late endosomes, respectively.

Our findings may provide novel insights into the links between familial and sporadic PD.Chaperone-mediated autophagy (CMA) and endosomal microautophagy (eMI) are pathways for selective degradation of cytosolic proteins in lysosomes and late endosomes, respectively. We propose that aberrant interactions of UCH-L1 variants with CMA machinery, at least partly, underlie the pathogenesis of I93M UCH-L1-associated PD, and possibly of sporadic PD. The interactions of UCH-L1 with LAMP-2A, Hsc70 and Hsp90 were also abnormally enhanced by carbonyl modification of UCH-L1.

We found that the levels of these interactions were aberrantly increased by the I93M mutation, and that expression of I93M UCH-L1 in cells induced the CMA inhibition-associated increase in the amount of alpha-synuclein, a risk factor for PD. We recently reported that UCH-L1 physically interacts with LAMP-2A, the lysosomal receptor for chaperone-mediated autophagy (CMA), and Hsc70 and Hsp90, both of which can function as components of the CMA pathway. The I93M mutation in UCH-L1 is also associated with familial PD. Ubiquitin C-terminal hydrolase L1 (UCH-L1) is expressed abundantly in neurons and has been reported to be a major target of oxidative/carbonyl damage associated with sporadic Parkinson's disease (PD).

Relationship between cip2a and chaperone mediated autophagy