Contact Information
| Postal |
Email |
Phone |
Web |
Gilmer
Hall, 229
Department of Biology
PO Box 400328
University of Virginia
Charlottesville, VA
22904-4328 |
gsb4g@virginia.edu |
Office:
(434)243-3543
Lab:
(434)243-3544 |
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Here |
Research Interests
Cellular
Morphogenesis and Moltility; Cell Biology of Alzheimer's Disease
| Research in our laboratory
is now focused primarily on two areas: the functions and regulation
of proteins known as IQGAPs, and the cell biological basis of
Alzheimer's disease (AD). We are also devoting a modest effort
to study intracellular trafficking of caveolin-1.
IQGAPs are large
scaffolding proteins that are intimately involved in controlling
cell motility, morphogenesis and adhesion. Most of our work
so far with these proteins has been directed at IQGAP1, and
its role in coupling growth factor stimulation of cells to assembly
in the cell cortex of branched actin filament networks. These
networks function as the engines for plasma membrane protrusion
during cell migration, and our results have indicated that IQGAP1
is required for their formation in many cell types.
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The histopathological
hallmark of Alzheimer's disease is the presence in brain of
extracellular deposits containing ß-amyloid peptide fibrils
plus intraneuronal neurofibrillary tangles, which are filaments
composed of the protein, tau. The goal of our work on AD is
to decipher the metabolic link that connects ß-amyloid
and tau to damage neurons. We have found that tau expression
makes microtubules hypersensitive to pre-fibrillar forms of
ß-amyloid, and suspect that tau-dependent, ß-amyloid-induced
microtubule disassembly is a seminal event in AD pathogenesis
at the cellular level.
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Caveolin-1 is the
signature protein of cell surface caveolae, but we have found
that vesicles and tubules containing the protein move constitutively
along microtubules between the plasma membrane and various intacellular
locations. During their excursions through the cytoplasm, these
membrane transport intermediates frequently merge with membranes
of the clathrin-dependent endocytotic system, and their transport
is tightly controled by the actin-based motor protein, myosin
Vc.

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Selected Publications
- Bloom GS, and Goldstein
LSB. 1998. Cruising Along Microtubule Highways: How Membranes Move
Through the Secretory Pathway. JOURNAL OF CELL BIOLOGY 140:
1277-1280. (Read
pdf)
- Fullerton AT, Bau M-Y,
Conrad PA, and Bloom GS. 1998. In Vitro Reconstitution of
Microtubule Plus End-directed, GTPγS-Sensitive Motility of Golgi
Membranes. MOLECULAR BIOLOGY OF THE CELL: 2699-2714.
(Read
pdf)
View
Fragments Movie
View Tubules Movie
View GTPγS Movie
- Mateer SC, McDaniel
AE, Nicolas V, Habermacher GM, Lin M-JS, Cromer DA, King ME, and
Bloom GS. 2002. The Mechanism for Regulation of the F-actin Binding
Activity of IQGAP1 by Calcium/Calmodulin. JOURNAL OF BIOLOGICAL
CHEMISTRY 277: 12,324-12,333. (Read
pdf)
View Calcium Response Movie
View
Calcium Reversal Movie
- Mundy DI, Machleidt
T, Ying Y-S, Anderson RGW, and Bloom GS. 2002. Control of Caveolar
Membrane Traffic by Microtubules and the Actin Cytoskeleton. JOURNAL
OF CELL SCIENCE 115: 4327-4339. (Read
pdf)
View
Movies
- Yamaoka-Tojo M, Ushio-Fukai
M, Hilenski L, Dikalov SI, Chen YE, Tojo T, Fukai T, Fujimoto M,
Patrushev NA, Wang N, Bloom GS, and Alexander RW. 2004. IQGAP1,
a Novel VEGF Receptor Binding Protein Involved in Redox-dependent
Endothelial Migration and Proliferation. CIRCULATION RESEARCH
95: 276-283. (Read
pdf)
- Bloom GS, Ren K, and
Glabe CG. 2005. Cultured Cell and Transgenic Mouse Models for Tau
Patholgy Linked to ß-Amyloid BIOCHIMICA ET BIOPHYSICA ACTA
MOLECULAR BASIS OF DISEASE 1739: 116-124. (Read
pdf)
- Morris, LE, Bloom GS,
Frierson HF Jr., and Powell SM. 2005. Nucleotide Variants Within
the IQGAP1 Gene in Diffuse-Type Gastric Cancers. Genes, Chromosomes
and Cancer 42: 280-286. (Read
pdf)
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