Distinct Functions of Nuclear Distribution Proteins LIS1, Ndel1 and NudCL in Regulating Axonal Mitochondrial Transport

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Abstract

Synopsis

Nuclear distribution family proteins are critical components of cytoplasmic dynein complex. Here we studied functions of LIS1, Ndel1 and NudCL on axonal mitochondrial transport. LIS1 interacts with kinsein family protein KIF5b. Depletion of LIS1 suppresses mitochondrial motility in anterograde and retrograde directions. While inhibition of either Ndel1 or NudCL partially reduces retrograde mitochondrial motility, simultaneous inhibition of these two almost blocks retrograde transport. Our results uncover novel roles of LIS1, Ndel1 and NudCL in the transport of mitochondria.

Synopsis

Nuclear distribution family proteins are critical components of cytoplasmic dynein complex. Here we studied functions of LIS1, Ndel1 and NudCL on axonal mitochondrial transport. LIS1 interacts with kinsein family protein KIF5b. Depletion of LIS1 suppresses mitochondrial motility in anterograde and retrograde directions. While inhibition of either Ndel1 or NudCL partially reduces retrograde mitochondrial motility, simultaneous inhibition of these two almost blocks retrograde transport. Our results uncover novel roles of LIS1, Ndel1 and NudCL in the transport of mitochondria.

Synopsis

Neurons critically depend on the long-distance transport of mitochondria. Motor proteins kinesin and dynein control anterograde and retrograde mitochondrial transport, respectively in axons. The regulatory molecules that link them to mitochondria need to be better characterized. Nuclear distribution (Nud) family proteins LIS1, Ndel1 and NudCL are critical components of cytoplasmic dynein complex. Roles of these Nud proteins in neuronal mitochondrial transport are unknown. Here we report distinct functions of LIS1, Ndel1 and NudCL on axonal mitochondrial transport in cultured hippocampal neurons. We found that LIS1 interacted with kinsein family protein KIF5b. Depletion of LIS1 enormously suppressed mitochondrial motility in both anterograde and retrograde directions. Inhibition of either Ndel1 or NudCL only partially reduced retrograde mitochondrial motility. However, knocking down both Ndel1 and NudCL almost blocked retrograde mitochondrial transport, suggesting these proteins may work together to regulate retrograde mitochondrial transport through linking dynein-LIS1 complex. Taken together, our results uncover novel roles of LIS1, Ndel1 and NudCL in the transport of mitochondria in axons.

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