Wq. Yu et al., INHIBITION OF A MITOTIC MOTOR COMPROMISES THE FORMATION OF DENDRITE-LIKE PROCESSES FROM NEUROBLASTOMA-CELLS, The Journal of cell biology, 136(3), 1997, pp. 659-668
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.