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Role of Protein Kinase C (PKC) Isoforms in Regulation of Filopodia Dynamics

Pandey, Pratima

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2016, Master of Science (MS), Bowling Green State University, Biological Sciences.
Filopodia are the sensory appendages of the cell and have an important role in directing motility, wound healing, and axon pathfinding. Previous work showed that oncogenic transformation of epithelial cells was accompanied by the loss of filopodia. The role of filopodia as sites for adhesion and signaling is well known but the dynamics is poorly understood. The core of the filopodium is a parallel array of actin filaments.  Mallavarapu and Mitchison have proposed that filopodia are retracted by halting actin assembly at the tip of the filaments, whereupon the filaments disassemble at the opposite end. Based on previous work, it was postulated that the filopodia are affected by PKC activation in such a way that actin arrays are disassembled. To study this, synthetic peptides representing the hydrophobic segment of PKC and the effector domain of myristoylated alanine-rich C kinase substrate (MARCKS) were designed to block PKC’s effects. After treatment with peptides, cells were collected with and without a brief exposure to phorbol 12-myristate 13-acetate (PMA). PMA activates the classical and novel PKCs. The cells were evaluated by phase contrast microscopy. The mean percentage periphery of the cells covered with filopodia and the percentage of cells in a population showing filopodia were counted. When cells were treated with peptides alone, no effect was observed but when treated with PMA, PKC ε blocking peptide partially rescued the filopodia from destruction. This was significant in the t-test (P-value <0.025).  Because rescue was only pertinent to PMA-treated cells, and the same treatment had no effect on filopodia of untreated cells, I postulate that PKC ε works by a different mechanism than that governing regular dynamics. I also studied the effect of protein tyrosine phosphatase (PTP) inhibitors on filopodia. The PTP1B inhibitor enhanced filopodia in both PMA-treated and -untreated conditions. The TC-PTP inhibitor did not affect cells treated with it alone but, when PMA-treated, prevented filopodia from disassembly.  The data for PTP inhibitors, like that for the synthetic peptides, suggests there may be an active mechanism of filopodia disassembly.  Thus, a mechanism of disassembly in addition to the Mallavarapu mechanism may exist.
Carol Heckman, PhD (Advisor)
Neocles Leontis, PhD (Committee Member)
Zhaohui Xu, PhD (Committee Member)
95 p.

Recommended Citations

Citations

  • Pandey, P. (2016). Role of Protein Kinase C (PKC) Isoforms in Regulation of Filopodia Dynamics [Master's thesis, Bowling Green State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1451317928

    APA Style (7th edition)

  • Pandey, Pratima. Role of Protein Kinase C (PKC) Isoforms in Regulation of Filopodia Dynamics. 2016. Bowling Green State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1451317928.

    MLA Style (8th edition)

  • Pandey, Pratima. "Role of Protein Kinase C (PKC) Isoforms in Regulation of Filopodia Dynamics." Master's thesis, Bowling Green State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1451317928

    Chicago Manual of Style (17th edition)