MOB: Pivotal Conserved Proteins in Cytokinesis, Cell Architecture and Tissue Homeostasis

SIMPLE SUMMARY: Multicellular organisms develop from a single cell into a multitude of cell types organized in tissues and organs. Organisms grow at a coordinated pace until reaching mature size. From this point, tissues and organs retain a constant size despite cell renovation. This depends on cell-cell communication and the constant integration of multiple signals, being regulated by several signaling pathways. The Hippo pathway stands out as it is also present in unicellular organisms. Some Hippo components control key cellular processes in unicellular organisms, like cell division and the perpetuation of cell morphology. Intrigued by this, we set out to understand the interplay between unicellular and multicellular Hippo regulation from the perspective of the most ancient proteins from this pathway, hereafter designated Monopolar spindle One Binder protein (MOB). We reviewed MOB functions along the tree of life to uncover its ancestral role, aiming to understand the origin of multicellularity. MOB-regulated cellular processes like division and death are essential for organism growth and tissues maintenance. The research on MOB of unicellular organisms highlighted the role of these proteins in the regulation of cell number and shape, critical issues for the maintenance of healthy tissues in multicellular organisms. This knowledge allows a better understanding of some human diseases like cancer. ABSTRACT: The MOB family proteins are constituted by highly conserved eukaryote kinase signal adaptors that are often essential both for cell and organism survival. Historically, MOB family proteins have been described as kinase activators participating in Hippo and Mitotic Exit Network/ Septation Initiation Network (MEN/SIN) signaling pathways that have central roles in regulating cytokinesis, cell polarity, cell proliferation and cell fate to control organ growth and regeneration. In metazoans, MOB proteins act as central signal adaptors of the core kinase module MST1/2, LATS1/2, and NDR1/2 kinases that phosphorylate the YAP/TAZ transcriptional co-activators, effectors of the Hippo signaling pathway. More recently, MOBs have been shown to also have non-kinase partners and to be involved in cilia biology, indicating that its activity and regulation is more diverse than expected. In this review, we explore the possible ancestral role of MEN/SIN pathways on the built-in nature of a more complex and functionally expanded Hippo pathway, by focusing on the most conserved components of these pathways, the MOB proteins. We discuss the current knowledge of MOBs-regulated signaling, with emphasis on its evolutionary history and role in morphogenesis, cytokinesis, and cell polarity from unicellular to multicellular organisms.