Expression of DDR1 in the CNS and in myelinating oligodendrocytes

Abstract

Discoidin domain receptor 1 (DDR1) is a tyrosine kinase receptor that is activated by fibrillar collagens. Here, we review the expression and role of DDR1 in the central nervous system (CNS). In a murine model, DDR1 is expressed in oligodendrocytes in the developing brain and during remyelination. In human adult brain tissue, DDR1 is detected in a similar pattern as other classical myelin proteins such as myelin basic protein (MBP). Up to 50 transcripts of DDR1 have been detected in human tissues, of which 5 isoforms have been identified. In the human brain, all 5 isoforms are detectable, but DDR1b is the most highly expressed, and DDR1c is coexpressed with myelin genes. DDR1 sequence variants have been associated with psychiatric disorders, and upregulation of this gene occurs in gliomas. Moreover, mutations in DDR1 have been found in tumors of Schwann cells, which are the myelinating cells of the peripheral nervous system. All these data suggest that DDR1 plays a role in myelination and is relevant to neuropsychiatric diseases.