INHIBITION OF A MITOTIC MOTOR COMPROMISES THE FORMATION OF DENDRITE-LIKE PROCESSES FROM NEUROBLASTOMA-CELLS

Microtubules in the axon are uniformly oriented, while microtubules in the dendrite are nonuniformly oriented. We have proposed that these d istinct microtubule polarity patterns may arise from a redistribution of molecular motor proteins previously used for mitosis of the develop ing neuroblast. To address this issue, we performed studies on neurobl astoma cells that undergo mitosis but also generate short processes du ring interphase. Some of these processes are similar to axons with reg ard to their morphology and microtubule polarity pattern, while others are similar to dendrites. Treatment with cAMP or retinoic acid inhibi ts cell division, with the former promoting the development of the axo n-like processes and the latter promoting the development of the dendr ite-like processes. During mitosis, the kinesin-related motor termed C H01/MKLP1 is localized within the spindle midzone where it is thought to transport microtubules of opposite orientation relative to one anot her. During process formation, CH01/ MKLP1 becomes concentrated within the dendrite-like processes but is excluded from the axon-like proces ses. The levels of CH01/MKLP1 increase in the presence of retinoic aci d but decrease in the presence of cAMP, consistent with a role for the protein in dendritic differentiation, Moreover, treatment of the cult ures with antisense oligonucleotides to CH01/MKLP1 compromises the for mation of the dendrite-like processes. We speculate that a redistribut ion of CH01/MKLP1 is required for the formation of dendrite-like proce sses, presumably by establishing their characteristic nonuniform micro tubule polarity pattern.