Suppression of Radixin and Moesin Alters Growth Cone Morphology, Motility, and Process Formation In Primary Cultured Neurons

doi:10.1083/jcb.143.2.443

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J. Cell Biol., Volume 143, Number 2, October 19, 1998 443-455

Suppression of Radixin and Moesin Alters Growth Cone Morphology, Motility, and Process Formation In Primary Cultured Neurons

Gabriela Paglini,^* Patricia Kunda,^* Santiago Quiroga, Kenneth Kosik,^§ and Alfredo Cáceres^*

^* Instituto Mercedes y Martin Ferreyra-CONICET, 5000 Cordoba, Argentina; Departamento Quimica Biologica (CIQUIBIC), Universidad Nacional Cordoba/CONICET, 5000 Cordoba, Argentina; and ^§ Department of Neurology (Neuroscience), Harvard Medical School, and Center for Neurological Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115

In this study we have examined the cellular functions of ERM proteins in developing neurons. The results obtained indicatethat there is a high degree of spatial and temporal correlationbetween the expression and subcellular localization of radixinand moesin with the morphological development of neuritic growthcones. More importantly, we show that double suppression of radixinand moesin, but not of ezrin-radixin or ezrin-moesin, resultsin reduction of growth cone size, disappearance of radial striations,retraction of the growth cone lamellipodial veil, and disorganizationof actin filaments that invade the central region of growth coneswhere they colocalize with microtubules. Neuritic tips from radixin-moesinsuppressed neurons displayed high filopodial protrusive activity;however, its rate of advance is 8-10 times slower than the oneof growth cones from control neurons. Radixin-moesin suppressedneurons have short neurites and failed to develop an axon-likeneurite, a phenomenon that appears to be directly linked withthe alterations in growth cone structure and motility. Taken collectively,our data suggest that by regulating key aspects of growth conedevelopment and maintenance, radixin and moesin modulate neuriteformation and the development of neuronal polarity.

Key words: ERM proteins; growth cones; actin filaments; neurite formation; axonal elongation

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