Thyroid hormone regulates the expression of the MAL proteolipid, a component of glycolipid-enriched membranes, in neonatal rat brain

Abstract

Detergent-insoluble glycosphingolipid-enriched membranes (DIGs) have been involved in the sorting and transport of specific proteins during oligodendrocyte maturation. The MAL (MAL, MVP17, VIP17) proteolipid, an integral membrane protein present in DIGs in mature oligodendrocytes, has been proposed as a component of the machinery for DIG-mediated transport in a restricted pattern of cell types including myelinating cells. We have previously shown that thyroid hormone regulates the expression of the myelin protein genes coordinately, and have suggested a major role for thyroid hormone in the control of oligodendrocytes generation. Here we show that the expression of the MAL gene is down-regulated by hypothyroidism and up-regulated by hyperthyroidism in myelinated regions of the brain. In contrast, adult-onset hypothyroidism has no effect on the steady-state levels of MAL mRNA. Taken together, our results show that MAL expression during oligodendrocyte maturation is modulated by thyroid hormone, suggesting that this hormone could play an important role in the myelin biogenesis during neonatal development.

Mechanisms for Nutrient Effects on Brain Development and Cognition

“…Progress in our understanding of thyroid hormone action in brain development over recent years has been made possible by the recognition of the central role of triiodothyronine in mediating thyroid hormone action and the recognition of specific nuclear receptors in target tissues as demonstrated by displacement studies. The cloning of the receptors and receptor variants has enabled investigators to undertake detailed analyses of the biochemical events that underlie the physiological and pathological action of thyroid hormone (TH) [24][25][26][27][28][29][30][31][32][33][34][35][36][37].…”

“…The expression of the MAL gene is down-regulated by hypothyroidism and up-regulated by hyperthyroidism in the myelinated regions of the brain. The MAL (MAL, MVP17, VIP17) proteolipid, an integral membrane protein, has been proposed as a component of the machinery necessary for myelin formation during oligodendrocyte maturation [37].…”

Isolation of MYADM, a novel hematopoietic-associated marker gene expressed in multipotent progenitor cells and up-regulated during myeloid differentiation

“…A possible site for phosphorylation of tyrosine residue 162 located in the loop between the fourth and fifth TM segments has also been identified. Significant similarity at the amino acid sequence level was only found to the MAL family of hydrophobic proteins, integral membrane proteins present in glycolipid-rich membranes in mature oligodendrocytes [35] and associated with human T cell differentiation [36]. The homology is between four stretches of approximately 20 amino acids representing the four TM-spanning domains present in the MAL protein and the first four TM domains in the MYADM protein.…”

Developmental Expression Pattern of the Myelin ProteolipiMAL Indicates Different Functions of MAL for Immature Schwann Cells and in a Late Step of CNS Myelinogenesis

“…MAL appeared even somewhat later ; we observed a delay of ~2‐3 days for mRNA and ~5‐6 days for MAL protein compared with MBP and PLP. Recently, it has been shown that MAL gene expression is regulated by thyroid hormone, as is known for many myelin proteins (Pombo et al, 1998). Our results suggest, however, the presence of a specific signal that determines the late onset of MAL expression, in addition to general stimuli.…”