We've updated our Privacy Policy to make it clearer how we use your personal data.

We use cookies to provide you with a better experience. You can read our Cookie Policy here.

Advertisement
Pathologic connection between LRRK2 & chaperone-mediated autophagy
Product News

Pathologic connection between LRRK2 & chaperone-mediated autophagy

Pathologic connection between LRRK2 & chaperone-mediated autophagy
Product News

Pathologic connection between LRRK2 & chaperone-mediated autophagy


Want a FREE PDF version of This Product News?

Complete the form below and we will email you a PDF version of "Pathologic connection between LRRK2 & chaperone-mediated autophagy"

First Name*
Last Name*
Email Address*
Country*
Company Type*
Job Function*
Would you like to receive further email communication from Technology Networks?

Technology Networks Ltd. needs the contact information you provide to us to contact you about our products and services. You may unsubscribe from these communications at any time. For information on how to unsubscribe, as well as our privacy practices and commitment to protecting your privacy, check out our Privacy Policy

Mutations in the LRRK2 gene are the most common cause of familial form of Parkinson’s disease (PD). LRRK2 exerts its toxic effect partly by blocking chaperone-mediated autophagy (CMA).


Wild type LRRK2 is readily digested by the lysosomes via CMA, however, its disease-causing variants are poorly degraded by this pathway (Orenstein et al., Nature Neuroscience 2013).


CMA-mediated degradation of LRRK2 requires binding to cytosolic chaperone hsc70, and recognition of hsc70-LRRK2 complex by LAMP2A on the lysosomal membrane. This interaction leads to the oligomerization of LAMP2A which forms a translocation complex that allows lysosomal import of LRRK2 and its proteolytic degradation within this compartment.


PD-related LRRK2 mutants block the oligomerization of LAMP2A and the formation of CMA translocation complex leading to impaired degradation and accumulation of LRRK2 and other CMA substrates including another PD-associated protein, α-synuclein. Interestingly, the toxic effect of LRRK2 on CMA is also manifested in cells that express high levels of the wild type protein, highlighting the need to tightly regulate its intracellular levels.


BioLegend
Learn more about BioLegend’s highly specific antibodies for LRRK2 and CMA-related proteins


BioLegend


Advertisement