Project Details


Two-photon laser scanning microscopy, fluorescence spectroscopy, molecular
biology, and biochemical approaches will be used to elucidate how 3-OH
phosphoinositide regulate the intracellular behavior of Cytohesin-1, whose
physiological role has been suggested to be the regulation of adhesion
through its interaction with the beta2 subunit of integrin receptors in
leukocytes. Integrins arbitrate communications between the cell and its
external environment in regulation of many cellular functions, including
embryonic development, tumor cell growth and metastasis, programmed cell
death, and leukocyte homing. Altered regulation of cellular adhesion can
also contribute to a number of disorders, among them rheumatoid arthritis,
cardiovascular disease, and cancer. The physiological importance of
leukocyte integrins is underscored by the finding that individuals lacking
the beta2 subunit suffer from a severe syndrome, leukocyte adhesion
deficiency, characterized by an inability to clear pathogens, recurrent
infections, and frequently, death at an early age. The proposal consists
of three specific aims: i) To determine if the Pleckstrin Homology (PH)
domain of Cytohesin-1 is required to recruit Cytohesin-1 to a cellular
membrane surface. ii) To determine if binding of the Cytohesin-I PH domain
to a specific 3-OH phosphoinositide is sufficient to recruit Cytohesin-1
to a cellular membrane. iii) To determine whether binding of Cytohesin-1
to the plasma membrane is sufficient for it to co-localize with integrin
beta2 and/or with ADP Ribosylation Factor. This project is centered on
understanding how DE-phosphoinositide lipid second messengers may regulate
the spatial and temporal localization of Cytohesin-1 under receptor
Effective start/end date5/1/984/30/01


  • National Institute of General Medical Sciences
  • National Institute of General Medical Sciences: $37,516.00
  • National Institute of General Medical Sciences


  • Cancer Research
  • Cell Biology


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