scholarly journals Type I PIPK-α regulates directed cell migration by modulating Rac1 plasma membrane targeting and activation

2010 ◽  
Vol 190 (3) ◽  
pp. 479-479
Author(s):  
Wei-Ting Chao ◽  
Alexes C. Daquinag ◽  
Felicity Ashcroft ◽  
Jeannette Kunz
Keyword(s):  
Plasma Membrane ◽  
Cell Migration ◽  
Membrane Targeting ◽  
Type I ◽  
Directed Cell Migration

scholarly journals Type I PIPK-α regulates directed cell migration by modulating Rac1 plasma membrane targeting and activation

2010 ◽  
Vol 190 (2) ◽  
pp. 247-262 ◽  
Author(s):  
Wei-Ting Chao ◽  
Alexes C. Daquinag ◽  
Felicity Ashcroft ◽  
Jeannette Kunz
Keyword(s):  
Plasma Membrane ◽  
Cell Migration ◽  
Adhesion Formation ◽  
Physical Interaction ◽  
Type I ◽  
Membrane Ruffling ◽  
Actin Organization ◽  
Upstream Regulator ◽  
Directed Cell Migration ◽  
Rac1 Activity

Phosphatidylinositol-4,5-bisphosphate (PI4,5P2) is a critical regulator of cell migration, but the roles of the type I phosphatidylinositol-4-phosphate 5-kinases (PIPKIs), which synthesize PI4,5P2, have yet to be fully defined in this process. In this study, we report that one kinase, PIPKI-α, is a novel upstream regulator of Rac1 that links activated integrins to the regulation of cell migration. We show that PIPKI-α controls integrin-induced translocation of Rac1 to the plasma membrane and thereby regulates Rac1 activation. Strikingly, this function is not shared with other PIPKI isoforms, is independent of catalytic activity, and requires physical interaction of PIPKI-α with the Rac1 polybasic domain. Consistent with its role in Rac1 activation, depletion of PIPKI-α causes pronounced defects in membrane ruffling, actin organization, and focal adhesion formation, and ultimately affects the directional persistence of migration. Thus, our study defines the role of PIPKI-α in cell migration and describes a new mechanism for the spatial regulation of Rac1 activity that is critical for cell migration.

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

2008 ◽  
Vol 19 (8) ◽  
pp. 3180-3191 ◽  
Author(s):  
Kate M. Cooper ◽  
David A. Bennin ◽  
Anna Huttenlocher
Keyword(s):  
Cell Migration ◽  
Family Member ◽  
Actin Polymerization ◽  
Stable Population ◽  
Type I ◽  
Microtubule Network ◽  
Interacting Protein ◽  
Directed Cell Migration ◽  
Transferrin Uptake ◽  
Dynamin 2

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 PIPKIγ. 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.

scholarly journals The Transmembrane Domain of the Respiratory Syncytial Virus F Protein Is an Orientation-Independent Apical Plasma Membrane Sorting Sequence

2005 ◽  
Vol 79 (19) ◽  
pp. 12528-12535 ◽  
Author(s):  
Sean C. Brock ◽  
Josh M. Heck ◽  
Patricia A. McGraw ◽  
James E. Crowe
Keyword(s):  
Plasma Membrane ◽  
Membrane Proteins ◽  
Epithelial Cells ◽  
Transmembrane Domain ◽  
Apical Plasma Membrane ◽  
Membrane Targeting ◽  
Type I ◽  
F Protein ◽  
Secretory Transport ◽  
Syncytial Virus

ABSTRACT The processes that facilitate transport of integral membrane proteins though the secretory pathway and subsequently target them to particular cellular membranes are relevant to almost every field of biology. These transport processes involve integration of proteins into the membrane of the endoplasmic reticulum (ER), passage from the ER to the Golgi, and post-Golgi trafficking. The respiratory syncytial virus (RSV) fusion (F) protein is a type I integral membrane protein that is uniformly distributed on the surface of infected nonpolarized cells and localizes to the apical plasma membrane of polarized epithelial cells. We expressed wild-type or altered RSV F proteins to gain a better understanding of secretory transport and plasma membrane targeting of type I membrane proteins in polarized and nonpolarized epithelial cells. Our findings reveal a novel, orientation-independent apical plasma membrane targeting function for the transmembrane domain of the RSV F protein in polarized epithelial cells. This work provides a basis for a more complete understanding of the role of the transmembrane domain and cytoplasmic tail of viral type I integral membrane proteins in secretory transport and plasma membrane targeting in polarized and nonpolarized cells.

scholarly journals Membrane Targeting Properties of a Herpesvirus Tegument Protein-Retrovirus Gag Chimera

2000 ◽  
Vol 74 (18) ◽  
pp. 8692-8699 ◽  
Author(s):  
J. Bradford Bowzard ◽  
Robert J. Visalli ◽  
Carol B. Wilson ◽  
Joshua S. Loomis ◽  
Eric M. Callahan ◽  
...  
Keyword(s):  
Amino Acids ◽  
Plasma Membrane ◽  
Golgi Apparatus ◽  
Solution Structure ◽  
Chimeric Protein ◽  
Membrane Targeting ◽  
Heterologous Proteins ◽  
Gag Protein ◽  
Internal Membrane ◽  
Simplex Virus

ABSTRACT The retroviral Gag protein is capable of directing the production and release of virus-like particles in the absence of all other viral components. Budding normally occurs after Gag is transported to the plasma membrane by its membrane-targeting and -binding (M) domain. In the Rous sarcoma virus (RSV) Gag protein, the M domain is contained within the first 86 amino acids. When M is deleted, membrane association and budding fail to occur. Budding is restored when M is replaced with foreign membrane-binding sequences, such as that of the Src oncoprotein. Moreover, the RSV M domain is capable of targeting heterologous proteins to the plasma membrane. Although the solution structure of the RSV M domain has been determined, the mechanism by which M specifically targets Gag to the plasma membrane rather than to one or more of the large number of internal membrane surfaces (e.g., the Golgi apparatus, endoplasmic reticulum, and nuclear, mitochondrial, or lysosomal membranes) is unknown. To further investigate the requirements for targeting proteins to discrete cellular locations, we have replaced the M domain of RSV with the product of the unique long region 11 (UL11) gene of herpes simplex virus type 1. This 96-amino-acid myristylated protein is thought to be involved in virion transport and envelopment at internal membrane sites. When the first 100 amino acids of RSV Gag (including the M domain) were replaced by the entire UL11 sequence, the chimeric protein localized at and budded into the Golgi apparatus rather than being targeted to the plasma membrane. Myristate was found to be required for this specific targeting, as were the first 49 amino acids of UL11, which contain an acidic cluster motif. In addition to shedding new light on UL11, these experiments demonstrate that RSV Gag can be directed to internal cellular membranes and suggest that regions outside of the M domain do not contain a dominant plasma membrane-targeting motif.

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