Abstract
Microtubules (MTs) in the axon are nearly all oriented with plus-end-out, and this pattern of organization is important for regulating the morphology and cytoplasmic composition of the axon, and for defining the cargoes transported in the anterograde and retrograde directions in the axon. Over the past several years, studies on vertebrate neurons (and also insect neurons) have been conducted by many investigators to understand the mechanisms that establish this pattern and maintain it over the life of the neuron and in the face of potential corruption. Studies on cultured rat sympathetic neurons from superior cervical ganglia (and also insect neurons) have implicated sliding of MTs by cytoplasmic dynein as crucial not only for establishing the plus-end-out orientation of axonal MTs but also for clearing mal-oriented MTs from the axon. Studies on cultured rat hippocampal neurons have implicated TRIM46 and augmin, proteins that regulate the crosslinking and nucleation of MTs, respectively. Here we show that the axons of hippocampal neurons also require dynein-based mechanisms for regulating their MT polarity pattern; however, the axons of sympathetic neurons do not require either TRIM46 or augmin. We also show that, in hippocampal neurons but not sympathetic neurons, the axon's MT polarity pattern is corrupted when a portion of the available Kinesin-1 is pharmacologically shifted from organelle transport to MT sliding. Collectively these results indicate that the mechanisms that regulate the MT polarity pattern of the axon are not entirely the same for different kinds of neurons, even in the same animal.