Dynacortin facilitates polarization of chemotaxing cells

<p>Abstract</p> <p>Background</p> <p>Cell shape changes during cytokinesis and chemotaxis require regulation of the actin cytoskeletal network. Dynacortin, an actin cross-linking protein, localizes to the cell cortex and contributes to cortical resistance, thereby helping to define the cell shape changes of cytokinesis. Dynacortin also becomes highly enriched in cortical protrusions, which are sites of new actin assembly.</p> <p>Results</p> <p>We studied the effect of dynacortin on cell motility during chemotaxis and on actin dynamics <it>in vivo </it>and <it>in vitro</it>. Dynacortin enriches with the actin, particularly at the leading edge of chemotaxing cells. Cells devoid of dynacortin do not become as polarized as wild-type control cells but move with similar velocities as wild-type cells. In particular, they send out multiple pseudopods that radiate at a broader distribution of angles relative to the chemoattractant gradient. Wild-type cells typically only send out one pseudopod at a time that does not diverge much from 0° on average relative to the gradient. Though <it>dynacortin</it>-deficient cells show normal bulk (whole-cell) actin assembly upon chemoattractant stimulation, dynacortin can promote actin assembly <it>in vitro</it>. By fluorescence spectroscopy, co-sedimentation and transmission electron microscopy, dynacortin acts as an actin scaffolder in which it assembles actin monomers into polymers with a stoichiometry of 1 Dyn₂:1 actin under salt conditions that disfavor polymer assembly.</p> <p>Conclusion</p> <p>Dynacortin contributes to cell polarization during chemotaxis. By cross-linking and possibly stabilizing actin polymers, dynacortin also contributes to cortical viscoelasticity, which may be critical for establishing cell polarity. Though not essential for directional sensing or motility, dynacortin is required to establish cell polarity, the third core feature of chemotaxis.</p

Outcomes of a National Institute of Allergy and Infectious Diseases Workshop on Understanding HIV-Exposed but Seronegative Individuals

The fascinating conundrum that some individuals who are exposed to HIV in ways that would make viral transmission highly likely, yet are able to remain uninfected, has been appreciated for many years. As early as the late 1980s, reports of such individuals began appearing in the HIV/AIDS literature. Despite the critical importance of understanding possible mechanisms of natural HIV resistance for developing effective prevention strategies, numerous obstacles have prevented this essential area of scientific exploration from moving forward. The Workshop held on July 8–9, 2010 and supported by the Office of AIDS Research (OAR), the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute on Drug Abuse (NIDA) at the NIH hosted 200 participants and utilized the expertise of 42 AIDS researchers as invited speakers, session chairs, and discussion leaders for presentations and breakout sessions in an attempt to remove some of those obstacles. Accomplishments of the participants included developing a consensus for a new general term for the field, HIV-exposed seronegative (HESN), while recognizing the necessity to identify and utilize secondary descriptive criteria such as exposure level, risk group, duration of seronegativity, or natural resistance. Three key questions for future research were also identified by the group: (1) What is different in HESN versus those who get infected? (2) What is the immune response in HESN and is it just a marker of exposure or a correlate of protection? (3) What are the HESN host factors that help HESN resist infection? This report briefly summarizes the presentations, and describes future directions for addressing these questions and challenges