TMEM120A and B: Nuclear Envelope Transmembrane Proteins Important for Adipocyte Differentiation

<div><p>Recent work indicates that the nuclear envelope is a major signaling node for the cell that can influence tissue differentiation processes. Here we present two nuclear envelope trans-membrane proteins TMEM120A and TMEM120B that are paralogs encoded by the <i>Tmem120A</i> and <i>Tmem120B</i> genes. The TMEM120 proteins are expressed preferentially in fat and both are induced during 3T3-L1 adipocyte differentiation. Knockdown of one or the other protein altered expression of several genes required for adipocyte differentiation, <i>Gata3</i>, <i>Fasn</i>, <i>Glut4</i>, while knockdown of both together additionally affected <i>Pparg</i> and <i>Adipoq</i>. The double knockdown also increased the strength of effects, reducing for example <i>Glut4</i> levels by 95% compared to control 3T3-L1 cells upon pharmacologically induced differentiation. Accordingly, TMEM120A and B knockdown individually and together impacted on adipocyte differentiation/metabolism as measured by lipid accumulation through binding of Oil Red O and coherent anti-Stokes Raman scattering microscopy (CARS). The nuclear envelope is linked to several lipodystrophies through mutations in lamin A; however, lamin A is widely expressed. Thus it is possible that the TMEM120A and B fat-specific nuclear envelope transmembrane proteins may play a contributory role in the tissue-specific pathology of this disorder or in the wider problem of obesity.</p></div