LRRK2 is required for CD38-mediated NAADP-Ca²⁺ signaling and the downstream activation of TFEB (transcription factor EB) in immune cells.

ABSTRACT: CD38 is a cell surface receptor capable of generating calcium-mobilizing second messengers. It has been implicated in host defense and cancer biology, but signaling mechanisms downstream of CD38 remain unclear. Mutations in LRRK2 (leucine-rich repeat kinase 2) are the most common genetic cause of Parkinson disease; it is also a risk factor for Crohn disease, leprosy, and certain types of cancers. The pathogenesis of these diseases involves inflammation and macroautophagy/autophagy, processes both CD38 and LRRK2 are implicated in. Here, we mechanistically and functionally link CD38 and LRRK2 as upstream activators of TFEB (transcription factor EB), a host defense transcription factor and the master transcriptional regulator of the autophagy/lysosome machinery. In B-lymphocytes and macrophag

SUBMITTER: Nabar NR 

PROVIDER: S-EPMC8865229 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature