Monastrol, a selective inhibitor of the mitotic kinesin Eg5, induces a distinctive growth profile of dendrites and axons in primary cortical neuron cultures

Abstract

Various factors including some motor proteins regulate microtubule (MT) transport and influence the formation of neuronal processes. Eg5, a slow and non-processive (+)-end directed motor molecule, is expressed in developing and differentiated neurons. However, how Eg5 works in neurons is still elusive. Thus, we treated primary rat cortical neuron cultures with monastrol, a specific inhibitor of Eg5, to investigate its role in neurons. Immature neurons treated with monastrol extended longer processes than control within a few hours. After 3 days, immature neurons treated with monastrol had longer dendrites but slightly shorter axons than control. This difference in growth between dendrites and axons became more prominent as the cells differentiated until 5 days. Interestingly, MT distributions in the cell bodies of monastrol-treated neurons appeared somewhat circular surrounding the nucleus, while MTs in the cell bodies of control neurons were primarily distributed in the MT organizing center (MTOC) just beside the nucleus. In mature neurons, monastrol treatment induced the axonal clusters of tubulins, grossly not affecting dendrites. Taken together, we conclude that Eg5 acts distinctively on dendrites and axons in neurons and suggest a putative model of how Eg5 works distinctively on dendrites and axons.