Dataset Information

Paxillin contracts the osteoclast cytoskeleton.

ABSTRACT: Osteoclastic bone resorption depends upon the cell's ability to organize its cytoskeleton via the ?v?3 integrin and osteoclastogenic cytokines. Because paxillin associates with ?v?3, we asked if it participates in skeletal degradation. Unlike deletion of other ?v?3-associated cytoskeleton-regulating molecules, which impairs the cell's ability to spread, paxillin-deficient (Pax(-/-) ) osteoclasts, generated from embryonic stem cells, "superspread" in response to receptor activator of NF-?B ligand (RANKL) and form large, albeit dynamically atypical, actin bands. Despite their increased size, Pax(-/-) osteoclasts resorb bone poorly, excavating pits approximately one-third normal depth. Ligand-occupied ?v?3 or RANKL promotes paxillin serine and tyrosine phosphorylation, the latter via cellular sarcoma (c-Src). The abnormal Pax(-/-) phenotype is rescued by wild-type (WT) paxillin but not that lacking its LD4 domain. In keeping with the appearance of mutant osteoclasts, WT paxillin, overexpressed in WT cells, contracts the cytoskeleton. Most importantly, the abnormal phenotype of Pax(-/-) osteoclasts likely represents failed RANKL-mediated delivery of myosin IIA to the actin cytoskeleton via the paxillin LD4 domain but is independent of tyrosine phosphorylation. Thus, in response to RANKL, paxillin associates with myosin IIA to contract the osteoclast cytoskeleton, thereby promoting its bone-degrading capacity.

SUBMITTER: Zou W

PROVIDER: S-EPMC3494816 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Paxillin contracts the osteoclast cytoskeleton.

Zou Wei W Deselm Carl J CJ Broekelmann Thomas J TJ Mecham Robert P RP Vande Pol Scott S Choi Kyunghee K Teitelbaum Steven L SL

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20121201 12

Osteoclastic bone resorption depends upon the cell's ability to organize its cytoskeleton via the αvβ3 integrin and osteoclastogenic cytokines. Because paxillin associates with αvβ3, we asked if it participates in skeletal degradation. Unlike deletion of other αvβ3-associated cytoskeleton-regulating molecules, which impairs the cell's ability to spread, paxillin-deficient (Pax(-/-) ) osteoclasts, generated from embryonic stem cells, "superspread" in response to receptor activator of NF-κB ligand ...[more]

PMID: 22807029

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Project description:IntroductionThe majority of large public universities have exclusive pouring rights contracts with beverage companies that produce and market sugar-sweetened beverages. Pouring rights contracts contain provisions that conflict with recommendations from major public health organizations that institutions reduce sugar-sweetened beverage availability, marketing, and consumption. This study assessed the following among students at 3 public universities: student perception of pouring rights contracts (the extent to which they favored or opposed pouring rights contracts), the association between student socioeconomic characteristics and perception of pouring rights contracts, student estimates of pouring rights contract revenue, and the association between student pouring rights contract revenue estimates and perception of pouring rights contracts. To contextualize results, actual pouring rights contract revenue as a percentage of total revenues was estimated.MethodsA cross-sectional exploratory study was conducted among a convenience sample of 1,311 undergraduate sugar-sweetened beverages-consuming students recruited from 3 large and diverse public universities in Northern California. On an online questionnaire, undergraduate students indicated the extent to which they favored or opposed pouring rights contracts on a 10-point scale (oppose=1-5, favor=6-10) and provided a numeric estimate of the percentage of total university revenue they thought their university's pouring rights contract generated. Regression models were used to analyze differences in perception of pouring rights contracts by student socioeconomic characteristics and estimates of university revenues generated by pouring rights contracts. In addition, pouring rights contracts and financial reports were obtained from the 3 universities to estimate actual pouring rights contract revenue as a percentage of total revenues. Survey data were collected between August and November 2018 and analyzed in August 2022.ResultsA large majority of students (81%) opposed pouring rights contracts, and the opposition did not significantly differ by student socioeconomic characteristics, including by levels of food security, need-based financial aid, participation in federal food assistance or healthcare programs, parental education, or parental income (all ps>0.14). The median student estimate for pouring rights contract revenue as a percentage of total university revenue was 10%. In contrast, the estimated actual annual revenue generated from the pouring rights contracts ranged from 0.01% to 0.04% at these schools. Revenue estimates were not significantly associated with participants' opposition or favoring of pouring rights contracts (p=0.65).ConclusionsA large majority of students opposed pouring rights contracts, and this opposition was similar regardless of student socioeconomic characteristics or student estimates of pouring rights contract revenues. Students markedly overestimated (by >100-1,000-fold) the percentage of university revenue that came from pouring rights contracts. University administration should consider student views on pouring rights contracts when deciding whether to exit or continue with pouring rights contracts.

Dataset Information

Paxillin contracts the osteoclast cytoskeleton.

Publications

Paxillin contracts the osteoclast cytoskeleton.

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