LIMK1 Regulates Golgi Dynamics, Traffic of Golgi derived vesicles and Process Extension in Primary Cultured Neurons

SILVANA ROSSO THESE AUTHORS CONTRIBUTED EQUALLY TO THIS STUDY; FLAVIA BOLLATI THESE AUTHORS CONTRIBUTED EQUALLY TO THIS STUDY; MARIANO BISBAL; DIEGO PERETTI; TOMOYUKI SUMI; TOSHIKAZU NAKAMURA; SANTIAGO QUIROGA; ADRIANA FERREIRA; ALFREDO CACERES

AMER SOC CELL BIOLOGY

Año: 2004 vol. 15 p. 3433 - 3433

In this study, we examined the subcellular distribution and functions of LIMK1 in developing neurons. Confocal microscopy, subcellular fractionation, and expression of several epitope-tagged LIMK1 constructs revealed that LIMK1 is enriched in the Golgi apparatus and growth cones, with the LIM domain required for Golgi localization and the PDZ domain for its presence at neuritic tips. Overexpression of wild-type LIMK1 suppresses the formation of trans-Golgi derived tubules, and prevents cytochalasin D-induced Golgi fragmentation, whereas that of a kinase-defective mutant has the opposite effect. Transfection of wild-type LIMK1 accelerates axon formation and enhances the accumulation of Par3/Par6, insulin-like growth factor (IGF)1 receptors, and neural cell adhesion molecule (NCAM) at growth cones, whileinhibiting the Golgi export of synaptophysin-containing vesicles. These effects were dependent on the Golgi localization of LIMK1, paralleled by an incre