ParaplegiaERDros · Roles of spastic paraplegia proteins in organisation of axonal endoplasmic reticulum

Roles of spastic paraplegia proteins in organisation of axonal endoplasmic reticulum

"The basic functional and structural unit of nervous system is a specialized cell called a neuron, which consists of a cell body and projections known as dendrites and axons. To innervate targets far from the cell body, axons can travel many orders of magnitude longer than the diameter of the cell body. In some lengthy nerves in humans, axons can extend up to a meter. Various machineries are employed in long axons to maintain their form and function, and defects in these machineries could give rise to neuropathies, such as axon degeneration, paralysis, or numbness, depending on which axons are affected. How do axons maintain communication along such a distance and avoid dysfunction? Small cellular compartments called organelles supply energy and carry signals for axonal function, and can be transported within the axon. Another membrane-bound tubular organelle, endoplasmic reticulum (ER), can form a continuous network throughout the whole cell and so could conduct local or long-range signals like a ""neuron within a neuron"". However, the physiological function of ER in axons, the mechanisms that form it, and the relationship between its form and function, are all poorly understood. The importance of ER in axon maintenance is supported by the fact that different mutations affecting ER-shaping proteins can lead to hereditary spastic paraplegia (HSP), a motor neuron disease which features degeneration of corticospinal motor tract – some of the longest axons in the body. Therefore, we aim to understand the specific role of HSP proteins on axonal ER shaping, and the mechanisms underlying the role of ER in axon maintenance and dysfunction. We believe that studies on HSP causative genes which encode ER-localised proteins will shed light on the pathology of HSP disease and the ensuing potential therapy targets. By further investigation of ER morphogenesis and its roles in axon function, we aim to deepen our understanding of how the nervous system works. "

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