Citron-N is a neuronal Rho-associated protein involved in Golgi organization through actin cytoskeleton regulation.
The actin cytoskeleton is best known for its role during cellular morphogenesis. However, other evidence suggests that actin is also crucial for the organization and dynamics of membrane organelles such as endosomes and the Golgi complex. As in morphogenesis, the Rho family of small GTPases are key mediators of organelle actin-driven events, although it is unclear how these ubiquitously distributed proteins are activated to regulate actin dynamics in an organelle-specific manner. Here we show that the brain-specific Rho-binding protein Citron-N is enriched at, and associates with, the Golgi apparatus of hippocampal neurons in culture. Suppression of the whole protein or expression of a mutant form lacking the Rho-binding activity results in dispersion of the Golgi apparatus. In contrast, high intracellular levels induce localized accumulation of RhoA and filamentous actin, protecting the Golgi from the rupture normally produced by actin depolymerization. Biochemical and functional analyses indicate that Citron-N controls actin locally by assembling together the Rho effector ROCK-II and the actin-binding, neuron-specific, protein Profilin-IIa (PIIa). Together with recent data on endosomal dynamics, our results highlight the importance of organelle-specific Rho modulators for actin-dependent organelle organization and dynamics.
Dipartimento di Genetica, Biologia e Biochimica, Università Degli Studi di Torino Via Santena, 5 bis, Torino, Italy.
Paola
P
Camera
Jorge Santos
JS
da Silva
Gareth
G
Griffiths
Maria Gabriella
MG
Giuffrida
Luciana
L
Ferrara
Vanessa
V
Schubert
Sara
S
Imarisio
Lorenzo
L
Silengo
Carlos G
CG
Dotti
Ferdinando
F
Di Cunto
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D003285:Contractile Proteins; D005333:Fetus; D006056:Golgi Apparatus / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D051304:Profilins; D011485:Protein Binding / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D000199:Actins; D018797:Cell Cycle Proteins; D003285:Contractile Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; C495740:Pfn1 protein, rat; D051304:Profilins; D020033:Protein Isoforms; D011506:Proteins; C115635:citron-kinase; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein