Several molecules that act in the nervous system to regulate sleep and wake were first identified based on their transport effects in pigmented cells. I compiled a list of such molecules like melatonin, melanin-concentrating hormone, and pigment dispersing factor, etc. Molecules that induce pigment aggregation promote sleep whereas molecules that induce pigment dispersal promote wake. I call these Sleep and PIgment Regulating Factors SPIRFs. SPIRFs regulate organelle trafficking in both pigmentary models and neurons. I propose that cargo transport fulfills necessary sleep functions such as remodeling synapses and restoring homeostasis in the distribution of cell components. I put forth the hypothesis that sleep-promoting SPIRFs induce states of increased cargo movement towards the cell body, and propose that this function is a critical neuron maintenance task for which animals must sleep.
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