Biomedical subjects

Ian Macara

Publications and source records attributed to Ian Macara.

3 recordsLinked to original sources

PubMed2006

Maintenance and modulation of T cell polarity.

As T cells move through the lymphatics and tissues, chemokine receptors, adhesion molecules, costimulatory molecules and antigen receptors engage their ligands in the microenvironment and contribute to establishing and maintaining cell polarity. Cytoskeletal assemblies, surface proteins and vesicle traffic are essential components of polarity and probably stabilize the activity of lymphocytes that must negotiate their 'noisy' environment. An additional component of polarity is a family of polarity proteins in T cells that includes Dlg, Scrib and Lgl, as well as a complex of partitioning-defective proteins. Ultimately, the strength of a T cell response may rely on correct T cell polarization. Therefore, loss of polarity regulators or guidance cues may interfere with T cell activation.

Animals↗

PubMed2004

Multiple mechanisms regulate NuMA dynamics at spindle poles.

The large coiled-coil protein NuMA plays an essential role in organizing microtubule minus ends at spindle poles in vertebrate cells. Here, we use both in vivo and in vitro methods to examine NuMA dynamics at mitotic spindle poles. Using fluorescence recovery after photobleaching, we show that an exogenously expressed green-fluorescent-protein/NuMA fusion undergoes continuous exchange between soluble and spindle-associated pools in living cells. These dynamics require cellular energy and display an average half-time for fluorescence recovery of approximately 3 minutes. To explore how NuMA dynamics at spindle poles is regulated, we exploited the association of NuMA with microtubule asters formed in mammalian mitotic extracts. Using a monoclonal antibody specific for human NuMA, we followed the fate of human NuMA associated with microtubule asters upon dilution with a hamster mitotic extract. Consistent with in vivo data, this assay shows that NuMA can be displaced from the core of pre-assembled asters into the soluble pool. The half-time of NuMA displacement from asters under these conditions is approximately 5 minutes. Using this assay, we show that protein kinase activity and the NuMA-binding protein LGN regulate the dynamic exchange of NuMA on microtubule asters. Thus, the dynamic properties of NuMA are regulated by multiple mechanisms including protein phosphorylation and binding to the LGN protein, and the rate of exchange between soluble and microtubule-associated pools suggests that NuMA associates with an insoluble matrix at spindle poles.

Animals↗

PubMed2003

Quantitative cell biology with the Virtual Cell.

Cell biological processes are controlled by an interacting set of biochemical and electrophysiological events that are distributed within complex cellular structures. Computational models, comprising quantitative data on the interacting molecular participants in these events, provide a means for applying the scientific method to these complex systems. The Virtual Cell is a computational environment designed for cell biologists, to facilitate the construction of models and the generation of predictive simulations from them. This review summarizes how a Virtual Cell model is assembled and describes the physical principles underlying the calculations that are performed. Applications to problems in nucleocytoplasmic transport and intracellular calcium dynamics will illustrate the power of this paradigm for elucidating cell biology.

Active Transport, Cell Nucleus↗