title: Mouse macrophage polarity and ROCK1 activity depend on RhoA and non-apoptotic Caspase 3.
abstract: The macrophages have different subtypes with different functions in immune response and disease. It has been generally accepted that M1 macrophages are responsible for stimulation of immune system and inflammation while M2 macrophages play a role in tissue repair. Irrespective of the type, macrophage functions depend on actin cytoskeleton, which is under the control of small GTPase RhoA pathway and its downstream effector ROCK1. We generated RhoA-deleted macrophages and compared the effect of RhoA deletion on M0, M1 and M2 macrophage phenotype. Our studies showed that, unexpectedly, the RhoA deletion did not eliminate macrophage ROCK1 expression and increased ROCK1 activity. The RhoA deletion effect on macrophage phenotype, structure and polarity was different for each subtype. Moreover, our study indicates that the up-regulation of ROCK1 activity in RhoA-deleted macrophages and macrophage phenotype/polarity are dependent on non-apoptotic Caspase-3 and are sensitive to Caspase-3 inhibition. These novel findings will revise/complement our understanding of RhoA pathway regulation of cell structure and polarity.
authors.affiliation: The Houston Methodist Research Institute, Houston, TX, USA; Department of Surgery, The Houston Methodist Hospital, Houston, TX, USA; Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China.
authors.forename: Yianzhu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Houston Methodist Research Institute, Houston, TX, USA; Department of Surgery, The Houston Methodist Hospital, Houston, TX, USA.
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Minze
authors.affiliation: The Houston Methodist Research Institute, Houston, TX, USA; Department of Surgery, The Houston Methodist Hospital, Houston, TX, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Mumma
authors.affiliation: The Houston Methodist Research Institute, Houston, TX, USA; Department of Surgery, The Houston Methodist Hospital, Houston, TX, USA.
authors.forename: Xian C
authors.initials: XC
authors.lastname: Li
authors.affiliation: The Houston Methodist Research Institute, Houston, TX, USA; Department of Surgery, The Houston Methodist Hospital, Houston, TX, USA; Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX, USA.
authors.forename: Rafik M
authors.initials: RM
authors.lastname: Ghobrial
authors.affiliation: The Houston Methodist Research Institute, Houston, TX, USA; Department of Surgery, The Houston Methodist Hospital, Houston, TX, USA. Electronic address: mkloc@houstonmethodist.org.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kloc
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism*; D016764:Cell Polarity / Q000502:physiology*; D002478:Cells, Cultured; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: C515854:Rock1 protein, mouse; D054460:rho-Associated Kinases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020742:rhoA GTP-Binding Protein
keywords: Actin; Caspase-3; Hummingbird phenotype; Macrophage; ROCK1; RhoA