Palladin and regulation of actin crosslinking and dynamics

dc.contributor.author	Beck, Moriah
dc.contributor.author	Dixon, Richard
dc.contributor.author	Goicoechea, Silvia
dc.contributor.author	Murphy, Grant
dc.contributor.author	Otey, Carol
dc.contributor.author	Campbell, Sharon
dc.date.accessioned	2012-09-09T02:38:07Z
dc.date.available	2012-09-09T02:38:07Z
dc.date.issued	2012-08
dc.identifier.citation	Beck, Moriah, Dixon, Richard, Goicoechea, Silvia, Murphy, Grant, Otey, Carol, and Sharon Campbell. 2012. Palladin and regulation of actin crosslinking and dynamics. Protein Science, v.21 SI pp.172-173	en_US
dc.identifier.issn	0961-8368
dc.identifier.other	WOS:000307019800303
dc.identifier.uri	http://dx.doi.org/10.1002/pro.2113
dc.identifier.uri	http://hdl.handle.net/10057/5270
dc.description	Click on the DOI link below to access the article (may not be free).	en_US
dc.description.abstract	Palladin is a recently discovered actin-associated protein that appears to be involved in both normal cell migration and invasive cell motility. Recently, we demonstrated that palladin is able to both bind and bundle actin filaments directly and revealed that one of the immunoglobulin-like domains of palladin (Ig3) is a novel actin-binding domain. These results indicate that palladin occupies an unusual functional niche, as it possesses the properties of both an actin-crosslinking protein and a molecular scaffold that binds to multiple other actin-regulating proteins. In the work presented here, we determined the NMR solution structure of palladin’s Ig3 domain and identified two basic patches that are critical for actin-binding and bundling. The results we have obtained provide insight into the manner in which palladin binds and crosslinks actin filaments and suggest the importance of electrostatics in this interaction. Electrostatics are also a major determinant in actin polymerization, therefore we further present preliminary kinetic data that indicates palladin may also be capable of inducing actin polymerization. In addition, we examined whether the Ig3 domain of palladin is required for actin organization in a cellular context. In cells transfected with a full-length palladin construct containing a deletion of the actin-binding domain we observe dramatically altered cellular distribution of both palladin and actin, which suggests that this interaction is critical. These findings are critical for understanding the mechanism that palladin utilizes in promoting cell motility by identifying residues within the palladin Ig3 domain that are important for actin binding and bundling, but also points to a mechanism for actin filament crosslinking.	en_US
dc.description.sponsorship	Source of research support: NIH grants F32 CA139926-01 (MRB), 5RO1GM081505 and NSF MCB-1121365 (CAO) and 5RO1GM080568-04 (SLC) and COBRE (8P20GM103420), KINBRE (P20RRO16475), Flossie West Memorial Foundation Trust (MRB).	en_US
dc.language.iso	en_US	en_US
dc.publisher	Wiley-Blackwell	en_US
dc.relation.ispartofseries	Protein Science;v.21 SI
dc.title	Palladin and regulation of actin crosslinking and dynamics	en_US
dc.type	Abstract	en_US