This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term goal of our laboratory is to understand the mechanisms by which information is encoded within second messenger signals, including Ca2+ and cAMP. These signaling pathways are known to regulate diverse processes including cellular excitability, proliferation, and gene expression. Our understanding of Ca2+ signals has increased dramatically over the last 30 years, primarily due to the development of single-cell methods for measuring intracellular Ca2+. Our understanding of cAMP signals, however, has lagged behind, largely due to the lack of high-resolution, single-cell measurement techniques. Only recently have reliable approaches for measuring cAMP signals in single cells been developed. These approaches have provided an unprecedented view of cyclic nucleotide signals near the plasma membranes of several cell types. We have used these approaches to provide evidence suggesting that the effective diffusion coefficient of cAMP is considerably slower than had been previously thought (~10,000-fold slower movement than by free diffusion alone). In addition, elegant studies demonstrated that compartmentalized cAMP signals are critical for barrier function in pulmonary microvascular endothelial cells (PMVECs). Based upon these studies, we propose testing the following working hypothesis: phosphodiesterase activity, buffering, and anomalously slow cAMP diffusion localize cAMP signals in pulmonary microvascular endothelial cells.
| Ron, Amit; Azeloglu, Evren U; Calizo, Rhodora C et al. (2017) Cell shape information is transduced through tension-independent mechanisms. Nat Commun 8:2145 |
| Schaff, James C; Gao, Fei; Li, Ye et al. (2016) Numerical Approach to Spatial Deterministic-Stochastic Models Arising in Cell Biology. PLoS Comput Biol 12:e1005236 |
| Semenova, Irina; Ikeda, Kazuho; Resaul, Karim et al. (2014) Regulation of microtubule-based transport by MAP4. Mol Biol Cell 25:3119-32 |
| Novak, Igor L; Slepchenko, Boris M (2014) A conservative algorithm for parabolic problems in domains with moving boundaries. J Comput Phys 270:203-213 |
| Michalski, Paul J (2014) First demonstration of bistability in CaMKII, a memory-related kinase. Biophys J 106:1233-5 |
| Azeloglu, Evren U; Hardy, Simon V; Eungdamrong, Narat John et al. (2014) Interconnected network motifs control podocyte morphology and kidney function. Sci Signal 7:ra12 |
| Ditlev, Jonathon A; Mayer, Bruce J; Loew, Leslie M (2013) There is more than one way to model an elephant. Experiment-driven modeling of the actin cytoskeleton. Biophys J 104:520-32 |
| Acker, Corey D; Loew, Leslie M (2013) Characterization of voltage-sensitive dyes in living cells using two-photon excitation. Methods Mol Biol 995:147-60 |
| Loew, Leslie M; Hell, Stefan W (2013) Superresolving dendritic spines. Biophys J 104:741-3 |
| Blasius, T Lynne; Reed, Nathan; Slepchenko, Boris M et al. (2013) Recycling of kinesin-1 motors by diffusion after transport. PLoS One 8:e76081 |
Showing the most recent 10 out of 117 publications
