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Vol. 19, Issue 8, 3180-3191, August 2008

This Article Full Text Full Text (PDF) Supplemental Materials All Versions of this Article: E08-02-0225v1 19/8/3180    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Cooper, K. M. Articles by Huttenlocher, A. PubMed PubMed Citation Articles by Cooper, K. M. Articles by Huttenlocher, A.

The PCH Family Member Proline-Serine-Threonine Phosphatase–interacting Protein 1 Targets to the Leukocyte Uropod and Regulates Directed Cell Migration

Kate M. Cooper^*, David A. Bennin, and Anna Huttenlocher^,

*Cellular and Molecular Biology Program, Departments of Medical Microbiology and Immunology and Pediatrics, University of Wisconsin, Madison, WI 53706

Submitted February 29, 2008; Revised May 1, 2008; Accepted May 7, 2008
Monitoring Editor: Carole Parent

Pombe Cdc15 homology (PCH) family members have emerged as important regulators of membrane–cytoskeletal interactions. Here we show that PSTPIP1, a PCH family member expressed in hematopoietic cells, regulates the motility of neutrophil-like cells and is a novel component of the leukocyte uropod where it colocalizes with other uropod components, such as type I PIPKI. Furthermore, we show that PSTPIP1 association with the regulator of endocytosis, dynamin 2, and PSTPIP1 expression impairs transferrin uptake and endocytosis. We also show that PSTPIP1 localizes at the rear of neutrophils with a subpopulation of F-actin that is specifically detected by the binding of an F-actin probe that detects a more stable population of actin. Finally, we show that actin polymerization, but not the microtubule network, is necessary for the polarized distribution of PSTPIP1 toward the rear of the cell. Together, our findings demonstrate that PSTPIP1 is a novel component of the leukocyte uropod that regulates endocytosis and cell migration.

Address correspondence to: Anna Huttenlocher (huttenlocher{at}wisc.edu)

Abbreviations used: C5a, complement factor 5a; DIC, differential interference contrast microscopy; dHL-60, differentiated HL-60; fMLP, N-formyl-L-methionyl-L-leucyl-L-phenylalanine; PAPA, pyogenic sterile arthritis pyoderma gangrenosum and acne; PCH, Pombe Cdc15 homology; PIPKI, typeI phosphatidylinositol phosphate kinase; PSTPIP1, proline-serine-threonine phosphatase–interacting protein 1; SH3, Src homology 3; WASP, Wiskott-Aldrich syndrome protein; Utr-CH, calponin homology domain of utrophin.

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