MTSS1: beyond the integration of actin and membrane dynamics

MTSS1 is a ubiquitously expressed intracellular protein known mainly for its involvement in basic cellular processes, such as the regulation of actin organization and membrane architecture. MTSS1 has attracted much attention for its role as a tumor suppressor, being absent or expressed at reduced levels in advanced and metastasizing cancers. Occasionally, MTSS1 is, instead, upregulated in metastasis and, in some cases, even in primary tumors. In addition to these well-established functions of MTSS1 linked to its I-BAR- and WH2-domains, the protein is involved in modulating cell-cell contacts, cell differentiation, lipid metabolism, and vesicle formation and acts as a scaffolding protein for several E3 ubiquitin ligases. MTSS1 is classified as a housekeeping protein and is never mutated despite the several pathologic phenotypes linked to its dysregulation. Despite MTSS1's involvement in fundamental signaling pathways, MTSS1 gene ablation is not ubiquitously lethal, although it affects embryonic development. Due to MTSS1´s involvement in many seemingly disparate processes, with many cases lacking mechanistic explanations, we found it timely to review the recent data on MTSS1's role at the cellular level, as well as in health and disease, to direct further studies on this interesting multifunctional protein.