The role of the motor kinesin, KIF1C, in vascular smooth muscle cell podosome regulation
When prompted by extracellular stimuli, Vascular Smooth Muscle Cells(VSMCs) acquire a synthetic phenotype capable of Extra-Cellular Matrix (ECM) remodeling. This allows for VSMC infiltration into atherosclerotic plaques and significantly contributes to cardiovascular disease. Efficient ECM remodeling by synthetic VSMCs requires dynamic podosomes, which consist of actin cores and outer adhesive rings, and serve as sites for Matrix Metalloproteinase (MMP) exocytosis. It has been shown that intracellular trafficking network composed of microtubules (MTs) is necessary for podosome formation downstream of protein kinase C (PKC), and that the MT-dependent motor kinesin, KIF1C, is critical for this regulation (Kopp et al., 2006). However, the nature of the cargo delivered by KIF1C to podosomes, whether it is a signaling factor and/or a podosome building block, is unknown. Moreover, Kaverina lab preliminary data indicate that KIF1C itself localizes at the outer podosome ring without MT association, which is unusual for a kinesin motor and may indicates a specific, possibly motor-independent function, at this location. The goal of my project is to determine the role of KIF1C in VSMC podosome regulation. The major hypothesis is that KIF1C delivers and/or anchors essential molecules at podosome sites.