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Cell Rep. 2015 Feb 10;10(5):820-832. doi: 10.1016/j.celrep.2015.01.034. Epub 2015 Feb 5.

The Secreted Protein C1QL1 and Its Receptor BAI3 Control the Synaptic Connectivity of Excitatory Inputs Converging on Cerebellar Purkinje Cells.

Author information

1
Center for Interdisciplinary Research in Biology (CIRB), Collège de France; CNRS UMR 7241; and INSERM U1050, Paris 75005, France.
2
Institut des Neurosciences Cellulaires et Intégratives, CNRS UPR 3212, Université de Strasbourg, Strasbourg 67084, France.
3
Center for Interdisciplinary Research in Biology (CIRB), Collège de France; CNRS UMR 7241; and INSERM U1050, Paris 75005, France; Institut des Neurosciences Cellulaires et Intégratives, CNRS UPR 3212, Université de Strasbourg, Strasbourg 67084, France.
4
Neuroprotection du Cerveau en Développement (PROTECT), INSERM, UMR1141, Université Paris-Diderot, Sorbonne Paris-Cité, Paris 75019, France.
5
Center for Interdisciplinary Research in Biology (CIRB), Collège de France; CNRS UMR 7241; and INSERM U1050, Paris 75005, France. Electronic address: fekrije.selimi@college-de-france.fr.

Abstract

Precise patterns of connectivity are established by different types of afferents on a given target neuron, leading to well-defined and non-overlapping synaptic territories. What regulates the specific characteristics of each type of synapse, in terms of number, morphology, and subcellular localization, remains to be understood. Here, we show that the signaling pathway formed by the secreted complement C1Q-related protein C1QL1 and its receptor, the adhesion-GPCR brain angiogenesis inhibitor 3 (BAI3), controls the stereotyped pattern of connectivity established by excitatory afferents on cerebellar Purkinje cells. The BAI3 receptor modulates synaptogenesis of both parallel fiber and climbing fiber afferents. The restricted and timely expression of its ligand C1QL1 in inferior olivary neurons ensures the establishment of the proper synaptic territory for climbing fibers. Given the broad expression of C1QL and BAI proteins in the developing mouse brain, our study reveals a general mechanism contributing to the formation of a functional brain.

PMID:
25660030
DOI:
10.1016/j.celrep.2015.01.034
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