title: A novel role for IQGAP1 protein in cell motility through cell retraction.
abstract: IQGAP1 has emerged as a key component in the regulation of cytoskeleton dynamics during cell migration, maintenance of adherens junctions, microbial pathogenesis and intracellular trafficking. IQGAP1 is known to localize to the protruding edge of lamellipodia in a variety of cell types and interact with regulators of actin dynamics. Here, we provide evidence suggesting a novel role of IQGAP1 in cell motility through cell edge retraction. In some of the cell lines examined, IQGAP1 was markedly separated from WAVE localization suggesting IQGAP1 may localize to retracting edges. B16F10 mouse melanoma cells exhibited the most restricted separation in which the appearance of GFP-IQGAP1 correlated with cell edge retraction velocity and the disappearance of mCherry-Arp3. These results demonstrate that in some cell types IQGAP1 may function to promote cell retraction not lamellipodium edge protrusion. In addition, we examined co-localization of IQGAP1 with adhesion site markers, myosin IIA, calmodulin and IQGAP2. In areas rich in IQGAP1 there was decreased immunofluorescence staining of vinculin, paxillin and phosphorylated-tyrosine indicating adhesion site disassembly. Interestingly, calmodulin, but not myosin IIA or IQGAP2, co-localized with IQGAP1 in areas of cell retraction. Overall these results suggest a new role of IQGAP1, distinct form IQGAP2, in cell migration through up regulation of contractility and downregulation of adhesion sites potentially through calmodulin interaction.
authors.affiliation: Department of Pharmaceutical Sciences, Southern Illinois University School of Pharmacy, Edwardsville, IL 62026, USA.
authors.forename: Sahar
authors.initials: S
authors.lastname: Foroutannejad
authors.affiliation: Department of Pharmaceutical Sciences, Southern Illinois University School of Pharmacy, Edwardsville, IL 62026, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Rohner
authors.affiliation: Department of Pharmaceutical Sciences, Southern Illinois University School of Pharmacy, Edwardsville, IL 62026, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Reimer
authors.affiliation: Department of Pharmaceutical Sciences, Southern Illinois University School of Pharmacy, Edwardsville, IL 62026, USA.
authors.forename: Guim
authors.initials: G
authors.lastname: Kwon
authors.affiliation: Department of Pharmaceutical Sciences, Southern Illinois University School of Pharmacy, Edwardsville, IL 62026, USA. Electronic address: joschob@siue.edu.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Schober
mesh_terms: D000818:Animals; D002147:Calmodulin / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D051379:Mice; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism; D011554:Pseudopodia / Q000502:physiology; D020703:ras GTPase-Activating Proteins / Q000378:metabolism
chemical_list: D002147:Calmodulin; C101203:IQ motif containing GTPase activating protein 1; C484416:Iqgap2 protein, mouse; D020703:ras GTPase-Activating Proteins; D024507:Nonmuscle Myosin Type IIA
keywords: Actin; Calmodulin; Cell adhesion; Cell retraction; IQGAP1; IQGAP2
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