Cilia protein IFT88 regulates extracellular protease activity by optimizing LRP-1-mediated endocytosis.

ABSTRACT: Matrix protease activity is fundamental to developmental tissue patterning and remains influential in adult homeostasis. In cartilage, the principal matrix proteoglycan is aggrecan, the protease-mediated catabolism of which defines arthritis; however, the pathophysiologic mechanisms that drive aberrant aggrecanolytic activity remain unclear. Human ciliopathies exhibit altered matrix, which has been proposed to be the result of dysregulated hedgehog signaling that is tuned within the primary cilium. Here, we report that disruption of intraflagellar transport protein 88 (IFT88), a core ciliary trafficking protein, increases chondrocyte aggrecanase activity in vitro. We find that the receptor for protease endocytosis in chondrocytes, LDL receptor-related protein 1 (LRP-1), is unevenly distrib

SUBMITTER: Coveney CR 

PROVIDER: S-EPMC6219823 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature