IDENTIFICATION OF A MICROTUBULE-ASSOCIATED MOTOR PROTEIN ESSENTIAL FOR DENDRITIC DIFFERENTIATION

The quintessential feature of the dendritic microtubule array is its n onuniform pattern of polarity orientation. During the development of t he dendrite, a population of plus end-distal microtubules first appear s, and these microtubules are subsequently joined by a population of o ppositely oriented microtubules. Studies from our laboratory indicate that the latter microtubules are intercalated within the microtubule a rray by their specific transport from the cell body of the neuron duri ng a critical stage in development (Sharp, D.J., W. Yu, and P.W. Baas. 1995. J. Cell Biol. 130:93-104). In addition, we have established tha t the mitotic motor protein termed CHO1/MKLP1 has the appropriate prop erties to transport microtubules in this manner (Sharp, D.J., R. Kuriy ama, and P.W. Baas. 1996. J. Neurosci. 16:4370-4375). In the present s tudy we have sought to determine whether CHO1/MKLP1 continues to be ex pressed in terminally postmitotic neurons and whether it is required f or the establishment of the dendritic microtubule array. In situ hybri dization analyses reveal that CHO1/MKLP1 is expressed in postmitotic c ultured rat sympathetic and hippocampal neurons. Immunofluorescence an alyses indicate that the motor is absent from axons but is enriched in developing dendrites, where it appears as discrete patches associated with the microtubule array. Treatment of the neurons with antisense o ligonucleotides to CHO1/MKLP1 suppresses dendritic differentiation, pr esumably by inhibiting the establishment of their nonuniform microtubu le polarity pattern. We conclude that CHO1/MKLP1 transports microtubul es from the cell body into the developing dendrite with their minus en ds leading, thereby establishing the nonuniform microtubule polarity p attern of the dendrite.