title: Mertk deficiency affects macrophage directional migration via disruption of cytoskeletal organization.
abstract: Mertk belongs to the Tyro3, Axl and Mertk (TAM) family of receptor tyrosine kinases, and plays a pivotal role in regulation of cytoskeletal rearrangement during phagocytosis. Phagocytosis by either professional or non-professional phagocytes is impaired in the Mertk deficient individual. In the present study, we further investigated the effects of Mertk mutation on peritoneal macrophage morphology, attachment, spreading and movement. Mertk-mutated macrophages exhibited decreased attachment, weak spreading, loss of spindle-like body shape and lack of clear leading and trailing edges within the first few hours of culture, as observed by environmental scanning electron microscopy. Time-lapse video photography recording showed that macrophage without Mertk conducted mainly random movement with oscillating swing around the cell body, and lost the directional migration action seen on the WT cells. Western blotting showed a decreased phosphorylation of focal adhesion kinase (FAK). Immunocytochemistry revealed that actin filaments and dynamic protein myosin II failed to concentrate in the leading edge of migrating cells. Microtubules were localized mainly in one side of mutant cell body, with no clear MTOC and associated radially-distributed microtubule bundles, which were clearly evident in the WT cells. Our results suggest that Mertk deficiency affects not only phagocytosis but also cell shape and migration, likely through a common regulatory mechanism on cytoskeletons.
authors.affiliation: Beijing Institute of Ophthalmology, Beijing Tong-Ren Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Beijing Tong-Ren Eye Center, Beijing Tong-Ren Hospital, Capital Medical University, Beijing 100069, China; Beijing Ophthalmology and Visual Science Key Laboratory. Beijing 100069, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Wu
authors.affiliation: Beijing Tong-Ren Eye Center, Beijing Tong-Ren Hospital, Capital Medical University, Beijing 100069, China; Beijing Ophthalmology and Visual Science Key Laboratory. Beijing 100069, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: National Center for Nanoscience and Technology, Beijing 100190, China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Xie
authors.affiliation: Beijing Tong-Ren Eye Center, Beijing Tong-Ren Hospital, Capital Medical University, Beijing 100069, China; Beijing Ophthalmology and Visual Science Key Laboratory. Beijing 100069, China.
authors.forename: Jingxue
authors.initials: J
authors.lastname: Zhang
authors.affiliation: National Center for Nanoscience and Technology, Beijing 100190, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.affiliation: Beijing Institute of Ophthalmology, Beijing Tong-Ren Hospital, Capital Medical University, Beijing 100069, China; Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd, Louisville, KY 40202, United States of America.
authors.forename: Qingxian
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Beijing Institute of Ophthalmology, Beijing Tong-Ren Hospital, Capital Medical University, Beijing 100069, China; Beijing Tong-Ren Eye Center, Beijing Tong-Ren Hospital, Capital Medical University, Beijing 100069, China; Beijing Ophthalmology and Visual Science Key Laboratory. Beijing 100069, China.
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Lu
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D048430:Cell Shape; D003599:Cytoskeleton / Q000378:metabolism*; D055786:Gene Knockout Techniques; D017737:Macrophages, Peritoneal / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D010587:Phagocytosis; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction; D000076202:c-Mer Tyrosine Kinase
chemical_list: D011518:Proto-Oncogene Proteins; C490767:Mertk protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase