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Nat Neurosci. 2015 Jan;18(1):36-45. doi: 10.1038/nn.3893. Epub 2014 Dec 8.

PlexinA1 is a new Slit receptor and mediates axon guidance function of Slit C-terminal fragments.

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University of Lyon, University Claude Bernard Lyon 1, CGphiMC UMR CNRS 5534, Lyon, France.
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
1] INSERM, UMRS_U968, Institut de la Vision, Paris, France. [2] Sorbonne Universités, Université Pierre et Marie Curie (UPMC) University of Paris 06, Institut de la Vision, Paris, France. [3] CNRS, UMR_7210, Paris, France.
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.


Robo-Slit and Plexin-Semaphorin signaling participate in various developmental and pathogenic processes. During commissural axon guidance in the spinal cord, chemorepulsion by Semaphorin3B and Slits controls midline crossing. Slit processing generates an N-terminal fragment (SlitN) that binds to Robo1 and Robo2 receptors and mediates Slit repulsive activity, as well as a C-terminal fragment (SlitC) with an unknown receptor and bioactivity. We identified PlexinA1 as a Slit receptor and found that it binds the C-terminal Slit fragment specifically and transduces a SlitC signal independently of the Robos and the Neuropilins. PlexinA1-SlitC complexes are detected in spinal cord extracts, and ex vivo, SlitC binding to PlexinA1 elicits a repulsive commissural response. Analysis of various ligand and receptor knockout mice shows that PlexinA1-Slit and Robo-Slit signaling have complementary roles during commissural axon guidance. Thus, PlexinA1 mediates both Semaphorin and Slit signaling, and Slit processing generates two active fragments, each exerting distinct effects through specific receptors.

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