TIAM-1 differentially regulates dendritic and axonal microtubule organization in patterning neuronal development through its multiple domains

摘要

Axon and dendrite development require the cooperation of actin and microtubule cytoskeletons. Microtubules form a well-organized network to direct polarized trafficking and support neuronal processes formation with distinct actin structures. However, it is largely unknown how cytoskeleton regulators differentially regulate microtubule organization in axon and dendrite development. Here, we characterize the role of actin regulators in axon and dendrite development and show that the RacGEF TIAM-1 regulates dendritic patterns through its N-terminal domains and suppresses axon growth through its C-terminal domains. TIAM-1 maintains plus-end-out microtubule orientation in posterior dendrites and prevents the accumulation of microtubules in the axon. In somatodendritic regions, TIAM-1 interacts with UNC-119 and stabilizes the organization between actin filaments and microtubules. UNC-119 is required for TIAM-1 to control axon growth, and its expression levels determine axon length. Taken together, TIAM-1 regulates neuronal microtubule organization and patterns axon and dendrite development respectively through its different domains.