Hosted by the School of Biochemistry
Spatial control of membrane traffic is essential for the morphogenesis and maintenance of polarized cell types such as epithelia and neurons, and their physiological functions in tissue homeostasis and neurotransmission. Many advances have been made in understanding membrane traffic at points of origin (protein sorting, vesicle formation) and destination (vesicle docking and fusion). However, how movement on cytoskeletal polymers (microtubules, actin) is spatially oriented and regulated en route to destination is little understood. The septin GTPases comprise a large family of GTP-binding proteins, which multimerize into higher order structures that associate with distinct membrane domains, and populations of microtubules and actin filaments. Septins assemble into complexes of variable subunit composition and localization, and thereby, may constitute a code for the spatial organization of microtubules and the navigation of molecular motors and their cargo. Using in vitro motility and membrane trafficking assays in hippocampal neurons, we discovered a selective and differential regulation of kinesin and dyneins motors, and their cargos by microtubule-associated septins. In addition to navigating motor-cargo movement in the microtubule network, we found that microtubule-associated septins capture and steer the ends of other dynamic microtubules and actin filaments, providing a novel mechanism for the spatial organization of the cytoskeleton. Hence, septin can spatially regulate the directionality of membrane traffic independently of their direct effects on motor-driven transport. Overall, our work suggests that septins are a core GTPase module for the spatial organization and regulation of membrane traffic, the complexity and physiological significance of which have only begun to emerge.
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