title: Mob as tumor suppressor is activated at the cell membrane to control tissue growth and organ size in Drosophila.
abstract: Growth inhibition mediated by Hippo (Hpo) signaling is essential for tissue growth and organ size control in Drosophila. However, the cellular mechanism by which the core components like Mob as tumor suppressor (Mats) and Warts (Wts) protein kinase are activated is poorly understood. In this work, we found that the endogenous Mats is located at the plasma membrane in developing tissues. Membrane targeting constitutively activates Mats to promote apoptosis and reduce cell proliferation, which leads to reduced tissue growth and organ size. Moreover, the ability of membrane-targeted Mats to inhibit tissue growth required the wts gene activity and Wts kinase activity was increased by the activated Mats in developing tissues. Consistent with the idea that Mats is a key component of the Hpo pathway, Mats is required and sufficient to regulate Yki nuclear localization. These results support a model in which the plasma membrane is an important site of action for Mats tumor suppressor to control tissue growth and organ size.
authors.affiliation: Intercollege Graduate Degree Program in Cell and Developmental Biology, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Li-Lun
authors.initials: LL
authors.lastname: Ho
authors.forename: Xiaomu
authors.initials: X
authors.lastname: Wei
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimizu
authors.forename: Zhi-Chun
authors.initials: ZC
authors.lastname: Lai
mesh_terms: D000818:Animals; D017209:Apoptosis; D002462:Cell Membrane / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000201:enzymology / Q000254:growth & development* / Q000648:ultrastructure; D004789:Enzyme Activation; D004843:Epistasis, Genetic; D005123:Eye / Q000166:cytology / Q000648:ultrastructure; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D009929:Organ Size; D009928:Organ Specificity; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D013347:Subcellular Fractions / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D000099317:Hippo Kinases
chemical_list: D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; C499633:Mats protein, Drosophila; C093503:wts protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases