Glial transcytosis of a photoreceptor-secreted signaling protein, retinoschisin.
In vitro studies have clearly shown that signaling/guidance proteins can diffuse to their targets. However, it is unclear whether they can travel by diffusion in vivo, or if they are distributed in the tissue by an active mechanism. Retinoschisin, a signaling molecule related to neuropilins, is synthesized and secreted by photoreceptor cells in the outer retina; then it interacts with inner retinal cells contributing to synaptic organization and optic nerve fiber integrity. We developed an assay to examine how retinoschisin, which is secreted a distance away, reaches its inner retinal targets. We found that retinoschisin is preferentially taken up and carried into the inner retina from the retinal outer border (the photoreceptor side) by Müller cells (the main glial cells of the vertebrate retina). This transcytosis is disrupted by DL-alpha-aminoadipic acid, a Müller cell/glia-specific toxin. Our results suggest that glial uptake/transcytosis can provide an effective and precise alternative for distributing signaling molecules in the nervous system.
Reid
Silvia N M
SN
Jules Stein Eye Institute, UCLA School of Medicine Center for the Health Sciences, 100 Stein Plaza, Los Angeles, CA 90095-7008, USA. reiddrs@aol.com
Farber
Debora B
DB
D000818:Animals; D005136:Eye Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000378:metabolism*; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism*
D005136:Eye Proteins; C108726:RS1 protein, human