Cargo hold and delivery: Ankyrins, spectrins, and their functional patterning of neurons Damaris N. Lorenzo Department of Cell Biology and Physiology, The University of North Carolina at Chapel Abstract Hill, Chapel Hill, North Carolina The highly polarized, typically very long, and nonmitotic nature of neurons present Correspondence them with unique challenges in the maintenance of their homeostasis. This architec- Damaris N. Lorenzo, Department of Cell tural complexity serves a rich and tightly controlled set of functions that enables their Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC fast communication with neighboring cells and endows them with exquisite plasticity. 27599. The submembrane neuronal cytoskeleton occupies a pivotal position in orchestrating Email:
[email protected] the structural patterning that determines local and long-range subcellular specializa- Funding information tion, membrane dynamics, and a wide range of signaling events. At its center is the National Institute of Neurological Disorders and Stroke, Grant/Award Number: partnership between ankyrins and spectrins, which self-assemble with both remark- R01NS110810 able long-range regularity and micro- and nanoscale specificity to precisely position and stabilize cell adhesion molecules, membrane transporters, ion channels, and other cytoskeletal proteins. To accomplish these generally conserved, but often functionally divergent and spatially diverse, roles these partners use a combinatorial program of a couple of dozens interacting family members, whose code is not fully unraveled. In a departure from their scaffolding roles, ankyrins and spectrins also enable the delivery of material to the plasma membrane by facilitating intracellular transport. Thus, it is unsur- prising that deficits in ankyrins and spectrins underlie several neurodevelopmental, neu- rodegenerative, and psychiatric disorders.