title: Reggies/flotillins regulate cytoskeletal remodeling during neuronal differentiation via CAP/ponsin and Rho GTPases.
abstract: The reggies/flotillins were discovered as proteins upregulated during axon regeneration. Here, we show that expression of a trans-negative reggie-1/flotillin-2 deletion mutant, R1EA, which interferes with oligomerization of the reggies/flotillins, inhibited insulin-like growth factor (IGF)-induced neurite outgrowth in N2a neuroblastoma cells and impaired in vitro differentiation of primary rat hippocampal neurons. Cells expressing R1EA formed only short and broad membrane protrusions often with abnormally large growth cones. R1EA expression strongly perturbed the balanced activation of the Rho-family GTPases Rac1 and cdc42. Furthermore, focal adhesion kinase (FAK) activity was also enhanced by R1EA expression, while other signaling pathways like ERK1/2, PKC or PKB signaling were unaffected. These severe signaling defects were caused by an impaired recruitment of the reggie/flotillin-associated adaptor molecule CAP/ponsin to focal contacts at the plasma membrane. Thus, the reggies/flotillins are crucial for coordinated assembly of signaling complexes regulating cytoskeletal remodeling.
authors: Department of Biology, University of Konstanz, Developmental Neurobiology Group, Universitätsstrasse 10, D-78457 Konstanz, Germany. Matthiaslanghorst@email.de
authors: Matthias F
authors: MF
authors: Langhorst
authors: Friederike A
authors: FA
authors: Jaeger
authors: Stephanie
authors: S
authors: Mueller
authors: L
authors: L
authors: Sven Hartmann
authors: Georg
authors: G
authors: Luxenhofer
authors: Claudia A O
authors: CA
authors: Stuermer
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000502:physiology*; D019084:Fluorescent Antibody Technique, Indirect; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D017353:Gene Deletion; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008565:Membrane Proteins / Q000502:physiology*; D008840:Microfilament Proteins / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D016501:Neurites / Q000502:physiology; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D008840:Microfilament Proteins; C485184:enhanced green fluorescent protein; C106354:flotillins; C119201:ponsin; D049452:Green Fluorescent Proteins; D007334:Insulin-Like Growth Factor I; D051416:Focal Adhesion Protein-Tyrosine Kinases; D064413:3-Phosphoinositide-Dependent Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein