Publications by authors named "Jorie Aardema"

4 Publications

  • Page 1 of 1

Loss of the F-BAR protein CIP4 reduces platelet production by impairing membrane-cytoskeleton remodeling.

Blood 2013 Sep 23;122(10):1695-706. Epub 2013 Jul 23.

Department of Pediatrics, Robert H. Lurie Comprehensive Cancer Center and Children's Memorial Hospital, Northwestern Feinberg School of Medicine, Chicago, IL 60611, USA.

Megakaryocytes generate platelets through extensive reorganization of the cytoskeleton and plasma membrane. Cdc42 interacting protein 4 (CIP4) is an F-BAR protein that localizes to membrane phospholipids through its BAR domain and interacts with Wiskott-Aldrich Syndrome Protein (WASP) via its SRC homology 3 domain. F-BAR proteins promote actin polymerization and membrane tubulation. To study its function, we generated CIP4-null mice that displayed thrombocytopenia similar to that of WAS(-) mice. The number of megakaryocytes and their progenitors was not affected. However, the number of proplatelet protrusions was reduced in CIP4-null, but not WAS(-), megakaryocytes. Electron micrographs of CIP4-null megakaryocytes showed an altered demarcation membrane system. Silencing of CIP4, not WASP, expression resulted in fewer proplatelet-like extensions. Fluorescence anisotropy studies showed that loss of CIP4 resulted in a more rigid membrane. Micropipette aspiration demonstrated decreased cortical actin tension in megakaryocytic cells with reduced CIP4 or WASP protein. These studies support a new biophysical mechanism for platelet biogenesis whereby CIP4 enhances the complex, dynamic reorganization of the plasma membrane (WASP independent) and actin cortex network (as known for WASP and cortical actin) to reduce the work required for generating proplatelets. CIP4 is a new component in the highly coordinated system of megakaryocytic membrane and cytoskeletal remodeling affecting platelet production.
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http://dx.doi.org/10.1182/blood-2013-03-484550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3765055PMC
September 2013

Biochemical and functional significance of F-BAR domain proteins interaction with WASP/N-WASP.

Semin Cell Dev Biol 2013 Apr 4;24(4):280-6. Epub 2013 Feb 4.

Department of Pediatrics, Northwestern University Feinberg School of Medicine, United States.

The Bin-Amphiphysin-Rvs (BAR) domain family of proteins includes groups which promote positive (classical BAR, N-BAR, and F-BAR) and negative (I-BAR) membrane deformation. Of these groups, the F-BAR subfamily is the most diverse in its biochemical properties. F-BAR domain proteins dimerize to form a tight scaffold about the membrane. The F-BAR domain provides a banana-shaped, alpha-helical structure that senses membrane curvature. Different types of F-BAR domain proteins contain tyrosine kinase or GTPase activities; some interact with phosphatases and RhoGTPases. Most possess an SH3 domain that facilitates the recruitment and activation of WASP/N-WASP. Thus, F-BAR domain proteins affect remodeling of both membrane and the actin cytoskeleton. The purpose of this review is to highlight the role of F-BAR proteins in coupling WASP/N-WASP to cytoskeletal remodeling. A role for F-BAR/WASP interaction in human diseases affecting nervous, blood, and neoplastic tissues is discussed.
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http://dx.doi.org/10.1016/j.semcdb.2013.01.005DOI Listing
April 2013

BAR proteins in cancer and blood disorders.

Int J Biochem Mol Biol 2012 18;3(2):198-208. Epub 2012 May 18.

Remodeling of the membrane and cytoskeleton is involved in a wide range of normal and pathologic cellular function. These are complex, highly-coordinated biochemical and biophysical processes involving dozens of proteins. Serving as a scaffold for a variety of proteins and possessing a domain that interacts with plasma membranes, the BAR family of proteins contribute to a range of cellular functions characterized by membrane and cytoskeletal remodeling. There are several subgroups of BAR proteins: BAR, N-BAR, I-BAR, and F-BAR. They differ in their ability to induce angles of membrane curvature and in their recruitment of effector proteins. Evidence is accumulating that BAR proteins contribute to cancer cell invasion, T cell trafficking, phagocytosis, and platelet production. In this review, we discuss the physiological function of BAR proteins and discuss how they contribute to blood and cancer disorders.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388730PMC
October 2012

Sexually dimorphic regulation of inhibin beta B in establishing gonadal vasculature in mice.

Biol Reprod 2006 May 1;74(5):978-83. Epub 2006 Feb 1.

Department of Veterinary Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802, USA.

Sexually dimorphic differentiation of gonads is accomplished through balanced interactions between positive and negative regulators. One of the earliest features of gonadal differentiation is the divergent patterning of the vasculature. A male-specific coelomic vessel develops on the anterior to posterior of the XY gonad, whereas this vessel is absent in XX gonads. It is postulated that the testis-determining gene Sry controls formation of the coelomic vessel, but the exact molecular mechanism remains unknown. Here we reveal a novel role for inhibin beta B in establishing sex-specific gonad vasculature. In the testis, inhibin beta B contributes to proper formation of the coelomic vessel, a male-specific artery critical for testis development and, later in development, hormone transportation. On the other hand, in the ovary, inhibin beta B is repressed by WNT4 and its downstream target follistatin, leading to the absence of the coelomic vessel. When either Wnt4 or follistatin was inactivated, the coelomic vessel appeared ectopically in the XX ovary. However, when inhibin beta B was also removed in either the Wnt4-null or follistatin-null background, normal ovarian development was restored and no coelomic vessel was found. Our results indicate that the sex-specific formation of the coelomic vessel is established by positive components in the testis as well as an antagonizing pathway from the ovary. Inhibin beta B is strategically positioned at the intersection of these opposing pathways.
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http://dx.doi.org/10.1095/biolreprod.105.050286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1819406PMC
May 2006
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