Myelin is a product of myelinating cells: Schawnn cells in the peripheral nervous system (PNS) and oligodendrocytes in the central nervous system (CNS). The processes of these myelinating cells wrap around axon segments to form a sheath. This sheath possesses insulating properties, allowing rapid propagation of action potentials (the electrical signal propagated by nerve cells) between the myelinating cell intervening nodes. Without myelin insulation, axons would need a 10-30-fold increase in diameter to achieve comparable conduction velocities. At the onset of myelination, during development, large amounts of myelin-specific lipids and proteins are synthesised and transported to the developing myelin sheath. The major protein component of PNS and CNS myelin differs between the 2 nervous systems. However, some of the minor protein components, including the 4 transmembrane (TM)-domain-containing myelin and lymphocyte protein (MAL), are found in both systems. Outside the nervous system, MAL is also found in T-cells and some epithelial cells (e.g., kidney, stomach and thyroid) []. Glycosphingolipids are enriched in both epithelial cells and myelin, and are believed to decrease the permeability of lipid membranes to small molecules and increase the ability for membrane curvature. MAL co-purifies with glycosphingolipids in detergent-insoluble domains, suggesting a possible interaction. In Madin Darby Canine Kidney (MDCK) cells, MAL is found mainly in transport vesicles, and recent studies suggest that MAL is required for efficient vesicular transport of proteins across apical cell membranes []. In myelinating cells, MAL appears to play a similar role, interacting with glycosphingolipids to decrease membrane permeability; however, here this property most likely manifests itself as an improved insulating ability of the myelin []. In lymphocytes, however, MAL appears to act as a TM-linker protein in T-cell signal transduction, linking the cell surface glycosyl phosphatidylinositol anchored protein CD59 to the intracellular tyrosine kinase Lck [].
Myocardin-related transcription factor A (MRTFA, also known MKL1) is an actin-binding transcriptional coactivator whose localisation is regulated by its interaction with monomeric actin (G-actin) []. Its N-terminal domain consists of three tandem RPEL repeats, where the G-actin binding site and the nuclear localisation signal can be found [, ]. In the nucleus MAL associates with SRF (serum response factor) and activates transcription of SRF:MAL-dependent target genes []. It has been implicated in human diseases, such as acute megakaryocytic leukemia []and other cancers [].
Methylaspartate ammonia lyase (3-methylaspartase, MAL) is a homodimeric enzyme, catalyzing the magnesium-dependent reversible alpha,beta-elimination of ammonia from L-threo-(2S,3S)-3-methylaspartic acid to mesaconic acid. This reaction is part of the main catabolic pathway for glutamate. MAL belongs to the enolase superfamily of enzymes, characterized by the presence of an enolate anion intermediate which is generated by abstraction of the alpha-proton of the carboxylate substrate by an active site residue and is stabilized by coordination to the essential Mg2+ ion [, , ].
Secreted Ly-6/uPAR-related protein 1 (SLURP-1) belongs to the Ly-6/uPAR superfamily of receptor and secreted proteins. SLURP1 has antitumor activity. It was found to be a marker of late differentiation of the skin. SLURP1 is implicated in maintaining the physiological and structural integrity of the keratinocyte layers of the skin [, , ]. Defects in SLURP1 are a cause of Mal de Meleda (MDM); also known as keratosis palmoplantaris transgradiens of Siemens. MDM is a rare autosomal recessive skin disorder, characterised by diffuse transgressive palmoplantar keratoderma with keratotic lesions extending onto the dorsa of the hands and the feet (transgrediens) [, ].
Myocardin (Myocd) is a coactivator of serum response factor (SRF), which is a key regulator of the expression of smooth and cardiac muscle genes. Myocardin plays a crucial role in cardiogenesis and differentiation of the smooth muscle cell lineage (myogenesis) [, ]. It contains the RPEL repeats, which are monomeric globular actin (G-actin) binding elements. However, it binds to actin-related protein 5 (Arp5) instead of conventional actin, resulting in a significant suppression of Myocd activity [].Myocardin-related transcription factor A (MRTFA, also known MKL1) is an actin-binding transcriptional coactivator whose localisation is regulated by its interaction with monomeric actin (G-actin) []. Its N-terminal domain consists of three tandem RPEL repeats, where the G-actin binding site and the nuclear localisation signal can be found [, ]. In the nucleus MAL associates with SRF (serum response factor) and activates transcription of SRF:MAL-dependent target genes []. It has been implicated in human diseases, such as acute megakaryocytic leukemia []and other cancers [].MKL2 binds to and activates SRF (serum response factor) similar to myocardin and MKL1 [].This entry includes Myocardin and MKL/myocardin-like protein 1/2 (MKL1/2).
