Sally H. Zigmond

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Contact information
212 Kaplan Wing, Leidy Lab
415 University Avenue
Philadelphia, PA 19104
Office: (215) 898-4559
Fax: (215) 898-8780
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Description of Research Expertise

Research Interests

Cell motility, chemotaxis, regulation of actin polymerization.

Keywords: Cell motility, actin.

Description of Research

My long-term interest is the migration and chemotaxis of polymorphonuclear leukocytes, the cells that provide the first line of defense against bacterial infections. PMNs find the bacteria through chemotaxis, directed locomotion along a chemical gradient. Once they attach to the bacteria, they ingest and kill them. Chemotaxis also plays an important role in development, immune responses, wound healing and malignant metastases. Current efforts focus on the biochemistry of the cell's motile machinery. In particular, we are studying the signal transduction pathways through which chemoattractants stimulate actin polymerization.

Actin polymerization is required for cell locomotion and localized actin polymerization is required for chemotaxis of leukocytes. The GTPase Cdc42 induces actin polymerization in leukocyte extracts by stimulating the Arp2/3 complex to nucleate new actin filaments. The Cdc42-induced filaments elongate rapidly at their barbed ends. The net result is an increase in filament number and total F-actin level. Merely adding filaments with free barbed ends does not induce polymerization. Thus, it appears that the Arp2/3 complex nucleated filaments are, at least transiently, protected from capping proteins (Zigmond et al. 1998; Huang et al. 1999).

Ongoing studies examine various molecules that interact with barbed ends and/or capping protein. We find a mammalian version of CARMIL binds capping protein and lowers its affinity for barbed ends 10-fold. CARMIL enhances the polymerization induced in cell extract. We find the yeast formin Bni1p nucleates new actin filaments and binds to the filament barbed-end where it partially inhibits elongation (Pruyne et al. 2002 and Pring et al. 2002). Our data suggest that Bni1p is a processive cap, moving with the barbed end as the filament elongates or shrinks.

Selected Publications

Zigmond, Sally H.: Formin induced nucleation of actin filaments. Curr. Opin. Cell Biol. 16: 99-105, 2004.

Pring, M. M. Evangelista, C. Boone, C. Yang, and S. H. Zigmond : Mechanism of formin-induced nucleation of actin filaments. Biochemistry 42: 486-496, 2003.

Evangelista, M., S. Zigmond and C. Boone: Formins: signaling effectors for assembly and polarization of actin filaments. J. Cell Sci 116: 2603-11, 2003.

Pring M., L. Cassimeris, and S. H. Zigmond: An unexplained sequestration of latrunculin A is required in nutrophils for inhibition of actin polymerization. Cell Motil. Cytoskel. 52: 122-130, 2002.

Pruyne D., M. Evangelista, C. Yang, E. Bi, S. Zigmond, A. Bretscher, C. Boone.: Role of Formins in Actin Assembly: Nucleation and Barbed-End Association. Science. 297: 612-615, 2002.

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Last updated: 10/06/2004
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