Premium
Axo‐glial communication through neurexin‐neuroligin signaling regulates myelination and oligodendrocyte differentiation
Author(s) -
Proctor Dustin T.,
Stotz Stephanie C.,
Scott Lucas O. M.,
de la Hoz Cristiane L. R.,
Poon Kelvin W. C.,
Stys Peter K.,
Colicos Michael A.
Publication year - 2015
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22875
Subject(s) - biology , neuroligin , neurexin , microbiology and biotechnology , axon , gene knockdown , signal transduction , postsynaptic potential , neuroscience , inhibitory postsynaptic potential , biochemistry , excitatory postsynaptic potential , genetics , cell culture , receptor
Axonal transsynaptic signaling between presynaptic neurexin (NX) and postsynaptic neuroligin (NL) is essential for many properties of synaptic connectivity. Here, we demonstrate the existence of a parallel axo‐glial signaling pathway between axonal NX and oligodendritic (OL) NL3. We show that this pathway contributes to the regulation of myelinogenesis, the maintenance of established myelination, and the differentiation state of the OL using in vitro models. We first confirm that NL3 mRNA and protein are expressed in OLs and in OL precursors. We then show that OLs in culture form contacts with non‐neuronal cells exogenously expressing NL3's binding partners NX1α or NX1β. Conversely, blocking axo‐glial NX‐NL3 signaling by saturating NX with exogenous soluble NL protein (NL‐ECD) disrupts interactions between OLs and axons in both in vitro and ex vivo assays. Myelination by OLs is tied to their differentiation state, and we find that blocking NX‐NL signaling with soluble NL protein also caused OL differentiation to stall at an immature stage. Moreover, in vitro knockdown of NL3 in OLs with siRNAs stalls their development and reduces branching complexity. Interestingly, inclusion of an autism related mutation in the NL blocking protein attenuates these effects; OLs differentiate and the dynamics of OL‐axon signaling occur normally as this peptide does not disrupt NX‐NL3 axo‐glial interactions. Our findings provide evidence not only for a new pathway in axo‐glial communication, they also potentially explain the correlation between altered white matter and autism. GLIA 2015;63:2023–2039