Ermin, A Myelinating Oligodendrocyte-Specific Protein That Regulates Cell Morphology

Abstract

Oligodendrocytes form an insulating multilamellar structure of compact myelin around axons, thereby allowing rapid propagation of action potentials. Despite the considerable clinical importance of myelination, little is known about the molecular mechanisms that enable oligodendrocytes to generate their specialized membrane wrapping. Here, we used microarray expression profiling of oligodendrocyte-ablated mutant mice to identify new glial molecules that are involved in CNS myelination. This effort resulted in the identification of Ermin, a novel cytoskeletal molecule that is exclusively expressed by oligodendrocytes. Ermin appears at a late stage during myelination, and in the mature nerves, it is localized to the outer cytoplasmic lip of the myelin sheath and the paranodal loops. In cultured oligodendrocytes, Ermin becomes visible in well differentiated MBP-positive cells, where it is concentrated at the tip of F-actinrich processes (termed "Ermin spikes"). Ectopic expression of Ermin, but not of a mutant protein lacking its actin-binding domain, induced the formation of numerous cell protrusions and a pronounced change in cell morphology. Our results demonstrate that Ermin is a novel marker of myelinating oligodendroglia and suggest that it plays a role in cytoskeletal rearrangements during the late wrapping and/or compaction phases of myelinogenesis.

An improved mouse line for Cre-induced cell ablation due to diphtheria toxin A, expressed from the Rosa26 locus

“…We have previously established a mouse line (R26:lacZ/DT-A) enabling us to express DTA in a time-and tissue-specific manner (Brockschnieder et al, 2004). Although this mouse line has proven to be a very useful tool in many different experimental set-ups (Brockschnieder et al, 2006;Gosgnach et al, 2006), we have discovered that homozygous animals develop abnormalities before Cremediated recombination has taken place. In the present study, we provide strong evidence that the observed abnormalities are due to leaky expression of DTA.…”

Human myelin proteome and comparative analysis with mouse myelin

“…First, we compared our database with other studies, primarily the transcriptome database of OLs, neurons, and astrocytes that were isolated from rodent brains (8,(12)(13)(14)(15)(16)(17)(18). Among the 308 proteins, there were at least 111 proteins in our myelin proteome whose mRNA or protein was expressed by OLs (Fig.…”

“…Many of these transcripts are expressed at higher levels in OL-rich white over gray matter, shown as fold enrichment (i.e., W/G ratio). In addition, to help ascertain the cellular origins of the proteins identified in our proteome, the relative enrichment of their transcripts in purified OLs (red squares in column O), neurons (column N), or astrocytes (column A) was determined through analysis of the transcriptome database of Cahoy et al (8) and other studies (12)(13)(14)(15)(16)(17)(18) of OLs (tan squares in column O). Comparison of the identified proteins in this study with other myelin proteomes (4 -7) has confirmed more than 50% of the identified proteins and revealed the presence of 163 additional proteins in myelin that have not previously been reported in any other proteome (column U).…”

Phosphodiesterase-Iα/autotaxin's MORFO domain regulates oligodendroglial process network formation and focal adhesion organization

“…Oligodendroglial process network formation, characterized by the generation and remodeling of higher order branches and interconnections, is initialized by well-coordinated changes in the organization of the actin cytoskeleton (Wilson and Brophy, 1989;Richter-Landsberg, 2000;Song et al, 2001;Liu et al, 2003;Jiang et al, 2005;Williams et al, 2005;Brockschnieder et al, 2006;Nielsen et al, 2006). In non-process bearing, migratory cells such actin cytoskeletal changes are to a large extent controlled by two interdependent mechanisms: 1) modifications of the extracellular environment and 2) the recruitment, retention and dissociation of molecules from focal adhesions, i.e.…”