Effect of the microtubule-associated protein tau in dynamics of single-headed motor proteins KIF1A

J. SPARACINO; M.G. FARÍAS; P.W. LAMBERTI

Buenos Aires

Conferencia; XV Giambiagi Winter School. Information proccesing in biological systems: from cells to equations, and back.; 2013

Universidad de Buenos Aires

Intracellular transport is fundamental for cellular function, survival, and morphogenesis. Kinesin superfamily proteins (also known as KIFs) are important molecular motors that directionally transport cargoes along microtubules (MTs), including membranous organelles, protein complexes and mRNAs. Disruptions or defects of MT-based transport are observed in many neurodegenerative diseases. MTs are decorated with non-motile microtubule-associated proteins (MAPs) that promote MT assembly and play important roles in organizing the MT cytoskeleton.Kinesin proteins interfere with MAPs, being the latest able to inhibit active transport of cytoplasmic material. Kinesin competes with MAPs tobind to the MT surface and MAPs bound to MTs might also block the path of motor proteins. Tau is a mainly neuronal MAP, enriched in the axonal compartment that has been shown to inhibit plus end-directed transport of vesicles along MTs by kinesin. Tau reduces not only the attachment frequency of kinesin to MTs but also the distance that kinesin travels along the MT in a single run. It is also known that when single kinesin motors encounter tau patches on the MT, most of the motors detach from the MT surface.Motivated by experiments on kinesin-tau interactions [Dixit et al. Science 319, 1086 (2008)] we developed a stochastic model of interacting single-headed motor proteins KIF1A that also takes into account the interactions between motor proteins and tau molecules. Our model reproduce experimental observations and predicts significant effects of tau on bound time and run length which suggest an important role oftau in regulation of kinesin-based transport.