Sally H. Zigmond
Professor, Depts of Biology

Cell Biology and Physiology Program

Address

212 Kaplan Wing of Leidy Lab
415 University Ave
Philadelphia, PA 19104

Office tel.: 215 898-4559
Lab tel.: 215 898-9379
Fax: 215 898-8780
E-mail: szigmond@sas.upenn.edu

Link(s)

Dr. Zigmond's Dept of Biology Page

EDUCATION

Wellesley: BA (Biology), 1966.

Rockefeller University: PhD (Cell Biology), 1972.

Yale University Med School: Postdoctoral research (Chemotaxis).

RESEARCH INTERESTS

• Cell motility, chemotaxis, regulation of actin polymerization.

Key words: cell motility, actin.

Search PubMed for articles

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. (The movie attached shows PMN migration in the presence of homogeneous chemoattractant and in the later sequences to a gradient of chemotattractant that is first on the right side of the image and later at the top.) 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).

On going 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. (The animation attached shows our concept of processive capping by Bni1p).

RECENT PUBLICATIONS

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

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

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

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

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

Lab

Lab personnel:

Changsong Yang