Establishment and plasticity of neuronal polarity

A fundamental feature of neurons is that they possess a polarized morphology, typified by a single long axon and several short dendrites. This cellular polarity forms the basis for directionalized rapid signaling, and for bi-directional trophic signaling, in neuronal circuits. While a catalog of structural, molecular, and functional differences between axons and dendrites is accumulating, the mechanisms involved in the establishment of neuronal polarity (also referred to as axogenesis) are not well understood. Cytoskeletal components, including microtubules and actin filaments, and cytoskeleton-regulating proteins such as microtubule-associated proteins (MAPs), actin-binding proteins, and 'motor' proteins, likely play important roles in the establishment and maintenance of neuronal polarity. Polarized sorting of membranes and proteins occurs in neurons, and a better understanding of such sorting mechanisms will likely provide insight into the process of axogenesis. Calcium plays a pivotal role in the regulation of neurite elongation and growth cone motility. Studies in which intracellular calcium levels are measured and manipulated in embryonic neurons during the process of axogenesis suggest a necessary role for calcium gradients in the establishment of neuronal polarity. Experimental models in which developing neurons are induced to switch their polarity support central roles for calcium-regulated cytoskeletal reorganization and protein sorting in the process of axogenesis. Finally, recent findings suggest that mitochondria play an important role in organizing neuronal polarity, possibly by controlling local calcium and/or energy gradients. While considerable progress is being made in elucidating mechanisms that regulate neuronal polarity, the seminal event(s) underlying this process remain a mystery.