David Martinelli (UConn)

The pleiotropic C1Q-like proteins regulate both synapses and oligodendrocyte maturation

Host: Stefan Schulte-Merker

Synapses are the fundamental structural unit by which neurons communicate. The complement C1q-like (C1QL) family of proteins are highly evolutionarily conserved and have drawn significant interest for their function at synapses in the central nervous system, where they are expressed in a subset of neurons and promote synapse formation and/or maintenance. In the first part of the seminar, we investigate the mechanism by which C1QL proteins promote synapses and use a multidisciplinary approach to support the hypothesis that C1QL proteins complete a novel ternary trans-synaptic adhesion complex by binding to membrane-tethered protein partners in the synaptic cleft. We show in a representative circuit how C1QL3-positive synapses are important for regulating behaviors, such as the sleep/wake/arousal behaviors controlled by the hypothalamus. In the second part of the seminar, we show how a C1QL paralog is surprisingly expressed in a glia cell type: oligodendrocyte progenitor cells (OPCs). OPCs represent a source of new oligodendrocytes to replace those lost during injury or in diseases such as multiple sclerosis (MS). How OPCs are instructed to differentiate into oligodendrocytes is poorly understood, and for reasons presently unclear, resident pools of OPCs are progressively less utilized in MS. We show with various molecular genetic techniques that C1QL1 initiates a previously unrecognized signaling pathway to promote new oligodendrocyte production with relevance for possible novel therapies of demyelinating diseases.

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