Calmodulin and profilin coregulate axon outgrowth in <i>Drosophila</i>

Kim, You Seung; Furman, Senta; Sink, Helen; VanBerkum, Mark F. A.

doi:10.1002/neu.1013

Cited by 27 publications

(33 citation statements)

References 67 publications

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“…Activation of myosin by expression of constitutively active MLCK (ctMLCK) allows pCC/MP2 axons to ignore repulsive signals and cross the midline inappropriately (Kim et al, 2002b). However, reducing actin polymerization by mutations in chickadee, the Drosophila gene for Profilin, suppresses the midline crossing errors caused by reduction of either Robo or CaM (Kim et al, 2001). This indicates that regulation of actin polymerization is required in pCC/MP2 neurons for proper response to midline guidance cues.…”

Section: Introductionmentioning

confidence: 89%

“…The X-gal staining pattern indicates which balancer chromosome(s) is present in the embryo and therefore the genotype of the embryo. Abnormal midline guidance defects were scored in embryos lacking balancer chromosomes as Fasciclin II-positive axon bundles crossing the midline in stage 16 or 17 embryos (Fritz and VanBerkum, 2000;Kim et al, 2001). …”

Section: Methodsmentioning

confidence: 99%

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Regulation of Rho Family GTPases Is Required to Prevent Axons from Crossing the Midline

Fritz

VanBerkum

2002

Developmental Biology

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Rho family GTPases are ideal candidates to regulate aspects of cytoskeletal dynamics downstream of axon guidance receptors. To examine the in vivo role of Rho GTPases in midline guidance, dominant negative (dn) and constitutively active (ct) forms of Rho, Drac1, and Dcdc42 are expressed in the Drosophila CNS. When expressed alone, only ctDrac and ctDcdc42 cause axons in the pCC/MP2 pathway to cross the midline inappropriately. Heterozygous loss of Roundabout enhances the ctDrac phenotype and causes errors in embryos expressing dnRho or ctRho. Homozygous loss of Son-of-Sevenless (Sos) also enhances the ctDrac phenotype and causes errors in embryos expressing either dnRho or dnDrac. CtRho suppresses the midline crossing errors caused by loss of Sos. CtDrac and ctDcdc42 phenotypes are suppressed by heterozygous loss of Profilin, but strongly enhanced by coexpression of constitutively active myosin light chain kinase (ctMLCK), which increases myosin II activity. Expression of ctMLCK also causes errors in embryos expressing either dnRho or ctRho. Our data confirm that Rho family GTPases are required for regulation of actin polymerization and/or myosin activity and that this is critical for the response of growth cones to midline repulsive signals. Midline repulsion appears to require down-regulation of Drac1 and Dcdc42 and activation of Rho.

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Section: Introductionmentioning

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Regulation of Rho Family GTPases Is Required to Prevent Axons from Crossing the Midline

Fritz

VanBerkum

2002

Developmental Biology

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“…However, there is currently no way to completely block axon outgrowth, and most methods that produce a partial block also would cause other disruptions of the cytoskeleton (Kim et al, 2001;Lee and Kolodziej, 2002). As an alternative, we generated Mbs clones in a disconnected (disco) mutant background.…”

Section: Molecular Biology Of the Cellmentioning

confidence: 99%

Excessive Myosin Activity inMbsMutants Causes Photoreceptor Movement Out of theDrosophilaEye Disc Epithelium

Lee

Treisman

2004

MBoC

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Neuronal cells must extend a motile growth cone while maintaining the cell body in its original position. In migrating cells, myosin contraction provides the driving force that pulls the rear of the cell toward the leading edge. We have characterized the function of myosin light chain phosphatase, which down-regulates myosin activity, in Drosophila photoreceptor neurons. Mutations in the gene encoding the myosin binding subunit of this enzyme cause photoreceptors to drop out of the eye disc epithelium and move toward and through the optic stalk. We show that this phenotype is due to excessive phosphorylation of the myosin regulatory light chain Spaghetti squash rather than another potential substrate, Moesin, and that it requires the nonmuscle myosin II heavy chain Zipper. Myosin binding subunit mutant cells continue to express apical epithelial markers and do not undergo ectopic apical constriction. In addition, mutant cells in the wing disc remain within the epithelium and differentiate abnormal wing hairs. We suggest that excessive myosin activity in photoreceptor neurons may pull the cell bodies toward the growth cones in a process resembling normal cell migration. INTRODUCTIONThe cytoskeleton plays a variety of roles during development, allowing cells to change their shape, adhesive properties, and motility (Jamora and Fuchs, 2002). Two critical components of the cytoskeleton are actin and nonmuscle myosin II. The contractile activity of actomyosin complexes has been implicated in cell migration, epithelial sheet movements, cytokinesis, axon outgrowth, and cell adhesion (Maciver, 1996;Jacinto et al., 2002;Dent and Gertler, 2003). During migration of several cell types, myosin activity is required to retract the rear of the cell (Ridley et al., 2003).Nonmuscle myosin II consists of a hexamer of two myosin heavy chains (MHC), two myosin light chains (MLC), and two myosin regulatory light chains (MRLC) (Korn and Hammer, 1988). Phosphorylation of key serine and threonine residues on MRLC stimulates the ATPase activity of MHC and promotes its assembly into filaments, leading to stress fiber contraction (Adelstein and Conti, 1975;Craig et al., 1983;Umemoto et al., 1989;Katoh et al., 2001). Mutations in the Drosophila orthologs of these myosin subunits have provided insight into the developmental functions of myosin II. Mutations in zipper (zip), which encodes MHC, cause defects in cytokinesis, closure of the dorsal embryonic epidermis over the amnioserosa, axon patterning, and myofibril formation (Zhao et al., 1988;Young et al., 1993;Bloor and Kiehart, 2001). spaghetti squash (sqh), encoding MRLC, is required for cytokinesis, oogenesis, and imaginal disc eversion (Karess et al., 1991;Wheatley et al., 1995;Edwards and Kiehart, 1996;Jordan and Karess, 1997).Actin-binding proteins of the ezrin, radixin, and moesin (ERM) family are thought to link transmembrane proteins to the actin cytoskeleton (Bretscher, 1999). ERM proteins are activated by phosphorylation of a conserved threonine residue, which inhibits associati...

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“…chickadee mutants have defects in a variety of actin-dependent processes including nurse cell dumping (Cooley et al, 1992), spermatogenesis (Castrillon et al, 1993), and oogenesis and bristle formation (Verheyen and Cooley, 1994). Additionally, Profilin is required for cell migration events such as epithelial dorsal closure (DC) (Jasper et al, 2001) and axon guidance (Kim et al, 2001); it is also required for lamellipodial ruffling in S2 cells (Rogers et al, 2003). During DC, an epithelial sheet migrates across the underlying amnioserosa to establish tissue continuity by means of a contractile actin cable and actin-based processes (Jacinto et al, 2000;Kiehart et al, 2000;Millard and Martin, 2008).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional regulation of Profilin during wound closure in Drosophila larvae

Brock

Wang

Berger

et al. 2012

Journal of Cell Science

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SummaryInjury is an inevitable part of life, making wound healing essential for survival. In postembryonic skin, wound closure requires that epidermal cells recognize the presence of a gap and change their behavior to migrate across it. In Drosophila larvae, wound closure requires two signaling pathways [the Jun N-terminal kinase (JNK) pathway and the Pvr receptor tyrosine kinase signaling pathway] and regulation of the actin cytoskeleton. In this and other systems, it remains unclear how the signaling pathways that initiate wound closure connect to the actin regulators that help execute wound-induced cell migrations. Here, we show that chickadee, which encodes the Drosophila Profilin, a protein important for actin filament recycling and cell migration during development, is required for the physiological process of larval epidermal wound closure. After injury, chickadee is transcriptionally upregulated in cells proximal to the wound. We found that JNK, but not Pvr, mediates the increase in chic transcription through the Jun and Fos transcription factors. Finally, we show that chic-deficient larvae fail to form a robust actin cable along the wound edge and also fail to form normal filopodial and lamellipodial extensions into the wound gap. Our results thus connect a factor that regulates actin monomer recycling to the JNK signaling pathway during wound closure. They also reveal a physiological function for an important developmental regulator of actin and begin to tease out the logic of how the wound repair response is organized.

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Calmodulin and profilin coregulate axon outgrowth in Drosophila

Cited by 27 publications

References 67 publications

Regulation of Rho Family GTPases Is Required to Prevent Axons from Crossing the Midline

Regulation of Rho Family GTPases Is Required to Prevent Axons from Crossing the Midline

Excessive Myosin Activity inMbsMutants Causes Photoreceptor Movement Out of theDrosophilaEye Disc Epithelium

Transcriptional regulation of Profilin during wound closure in Drosophila larvae

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