Signaling function of alpha-catenin in microtubule regulation.
Centrosomes control microtubule dynamics in many cell types, and their removal from the cytoplasm leads to a shift from dynamic instability to treadmilling behavior and to a dramatic decrease of microtubule mass (Rodionov et al., 1999; PNAS 96:115). In cadherin-expressing cells, these effects can be reversed:non-centrosomal cytoplasts that form cadherin-mediated adherens junctions display dense arrays of microtubules (Chausovsky et al., 2000; Nature Cell Biol 2:797). In adherens junctions, cadherin's cytoplasmic domain binds p120 catenin and beta-catenin, which in turn binds alpha-catenin. To elucidate the roles of the cadherin-associated proteins in regulating microtubule dynamics, we prepared GFP-tagged, plasma membrane targeted or untargeted p120 catenin, alpha-catenin and beta-catenin and tested their ability to rescue the loss of microtubule mass caused by centrosomal removal in the poorly adhesive cell line CHO-K1. Only membrane targeting of alpha-catenin led to a significant increase in microtubule length and density in centrosome-free cytoplasts. Expression of non-membrane-targeted alpha-catenin produced only a slight effect, while both membrane-targeted and non-targeted p120 and beta-catenin were ineffective in this assay. Together, these findings suggest that alpha-catenin is able to regulate microtubule dynamics in a centrosome-independent manner.
Shtutman
Michael
M
Cancer Center, Ordway Research Institute, Albany, New York, USA. mshtutman@ordwayresearch.org
Chausovsky
Alexander
A
Prager-Khoutorsky
Masha
M
Schiefermeier
Natalia
N
Boguslavsky
Shlomit
S
Kam
Zvi
Z
Fuchs
Elaine
E
Geiger
Benjamin
B
Borisy
Gary G
GG
Bershadsky
Alexander D
AD
D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D018385:Centrosome / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D003593:Cytoplasm / Q000648:ultrastructure; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D015820:Cadherins; D051178:alpha Catenin