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A NOVEL REGULATORY ROLE OF TRAPPC9 IN L-PLASTIN-MEDIATED ACTIN RING FORMATION AND OSTEOCLAST FUNCTION

Hussein, Nazar J
http://orcid.org/0000-0001-7291-757X
http://rave.ohiolink.edu/etdc/view?acc_num=kent1480264440525728

Abstract Details

2016, MS, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.
Trafficking Protein Particle Complex 9 (TRAPPC9) is a major subunit of TRAPP Complex. TRAPPC9 has been reported to bind IKappaB Kinase (IKK2) NF-KappaB-inducing kinase (NIK) where it plays a role in the canonical and non-canonical of NFkB signaling in Osteoclast (OC) differentiation and function. Respectively, the role of TRAPPC9 in protein trafficking in OC has not been studied. In this study, we first examined the co-localization of TRAPPC9 with cathapsin-K (Cathp.K), known to mediate OC resorption suggesting that TRAPPC9 mediates the trafficking and function of OCs. Second, to identify TRAPPC9 protein partners important for OC-mediated bone resorption, we conducted immunoprecipitation of TRAPPC9 isolated from terminally differentiated OCs followed by mass spectrometry analysis. Surprisingly, our data showed that TRAPPC9 binds various protein partners. One of those proteins is L-Plastin (LPL). LPL is localized at the podosomes and plays a crucial role in actin aggregation thereby actin ring formation and OC function. Recent studies reported that LPL null OCs demonstrated normal OC differentiation phenotype and peripheral podosomes aggregation. However, significant disruption in actin ring formation and the sealing zone region were observed. Although the role of LPL in OC-mediated bone resorption has not reported in details. Here, we investigated the potential regulatory role of TRAPPC9 and LPL-mediated OC differentiation and function. Thereby, we assessed the localization of TRAPPC9 and LPL in OC and found that TRAPPC9 is co-localized with LPL within the periphery of OC. Next, we determined the effect of TRAPPC9 overexpression using viral system on LPL recruitment to the actin ring. Interestingly, our data showed that TRAPPC9 overexpression promotes the recruitment of LPL to the actin ring when compared to controlled cultures. This recruitment is associated with increasing OC-mediated bone resorption. In conclusion, our hypothesis is that TRAPPC9 plays a regulatory role in L-Plastin-mediated actin ring formation and osteoclast function and the overall objective of this research was to evaluate TRAPPC9/ LPL interaction as a possible target for modilities to enhance bone repair and regeneration.
Fayez Safadi (Advisor)
101 p.
Biomedical Research
Bone-Osteoclast-Osteoporosis-Cytoskeleton-Actin ring-Podosomes

Recommended Citations

Citations

  • Hussein, N. J. (2016). A NOVEL REGULATORY ROLE OF TRAPPC9 IN L-PLASTIN-MEDIATED ACTIN RING FORMATION AND OSTEOCLAST FUNCTION [Master's thesis, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1480264440525728

    APA Style (7th edition)

  • Hussein, Nazar. A NOVEL REGULATORY ROLE OF TRAPPC9 IN L-PLASTIN-MEDIATED ACTIN RING FORMATION AND OSTEOCLAST FUNCTION . 2016. Kent State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1480264440525728.

    MLA Style (8th edition)

  • Hussein, Nazar. "A NOVEL REGULATORY ROLE OF TRAPPC9 IN L-PLASTIN-MEDIATED ACTIN RING FORMATION AND OSTEOCLAST FUNCTION ." Master's thesis, Kent State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=kent1480264440525728

    Chicago Manual of Style (17th edition)

kent1480264440525728
836
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This open access ETD is published by Kent State University and OhioLINK.