title: Pak3 regulates apical-basal polarity in migrating border cells during Drosophila oogenesis.
abstract: Group cell migration is a highly coordinated process that is involved in a number of physiological events such as morphogenesis, wound healing and tumor metastasis. Unlike single cells, collectively moving cells are physically attached to each other and retain some degree of apical-basal polarity during the migratory phase. Although much is known about direction sensing, how polarity is regulated in multicellular movement remains unclear. Here we report the role of the protein kinase Pak3 in maintaining apical-basal polarity in migrating border cell clusters during Drosophila oogenesis. Pak3 is enriched in border cells and downregulation of its function impedes border cell movement. Time-lapse imaging suggests that Pak3 affects protrusive behavior of the border cell cluster, specifically regulating the stability and directionality of protrusions. Pak3 functions downstream of guidance receptor signaling to regulate the level and distribution of F-actin in migrating border cells. We also provide evidence that Pak3 genetically interacts with the lateral polarity marker Scribble and that it regulates JNK signaling in the moving border cells. Since Pak3 depletion results in mislocalization of several apical-basal polarity markers and overexpression of Jra rescues the polarity of the Pak3-depleted cluster, we propose that Pak3 functions through JNK signaling to modulate apical-basal polarity of the migrating border cell cluster. We also observe loss of apical-basal polarity in Rac1-depleted border cell clusters, suggesting that guidance receptor signaling functions through Rac GTPase and Pak3 to regulate the overall polarity of the cluster and mediate efficient collective movement of the border cells to the oocyte boundary.
authors.affiliation: Department of Biological Sciences, Indian Institute of Science Education & Research-Kolkata, Mohanpur Campus, Mohanpur 741246, Nadia, West Bengal, India.
authors.forename: Martina
authors.initials: M
authors.lastname: Felix
authors.affiliation: Department of Biological Sciences, Indian Institute of Science Education & Research-Kolkata, Mohanpur Campus, Mohanpur 741246, Nadia, West Bengal, India.
authors.forename: Mrinal
authors.initials: M
authors.lastname: Chayengia
authors.affiliation: Department of Biological Sciences, Indian Institute of Science Education & Research-Kolkata, Mohanpur Campus, Mohanpur 741246, Nadia, West Bengal, India.
authors.forename: Ritabrata
authors.initials: R
authors.lastname: Ghosh
authors.affiliation: Department of Biological Sciences, Indian Institute of Science Education & Research-Kolkata, Mohanpur Campus, Mohanpur 741246, Nadia, West Bengal, India.
authors.forename: Aditi
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Biological Sciences, Indian Institute of Science Education & Research-Kolkata, Mohanpur Campus, Mohanpur 741246, Nadia, West Bengal, India mohitprasad@iiserkol.ac.in.
authors.forename: Mohit
authors.initials: M
authors.lastname: Prasad
mesh_terms: D000818:Animals; D002465:Cell Movement; D016764:Cell Polarity; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D008565:Membrane Proteins; D009866:Oogenesis; D015398:Signal Transduction; D059008:Time-Lapse Imaging; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; C090146:Rac1 protein, Drosophila; C404683:Scrib protein, Drosophila; D025521:Tumor Suppressor Proteins; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins
keywords: Apical-basal polarity; Border cell movement; Collective cell migration; Drosophila Pak3