WNK1 kinase balances T cell adhesion versus migration in vivo

Adhesion and migration of T cells are controlled by chemokines and by adhesion molecules, especially integrins, and have critical roles in the normal physiological function of T lymphocytes. Using an RNA-mediated interference screen, we identified the WNK1 kinase as a regulator of both integrin-mediated adhesion and T cell migration. We found that WNK1 is a negative regulator of integrin-mediated adhesion, whereas it acts as a positive regulator of migration via the kinases OXSR1 and STK39 and the ion co-transporter SLC12A2. WNK1-deficient T cells home less efficiently to lymphoid organs and migrate more slowly through them. Our results reveal that a pathway previously known only to regulate salt homeostasis in the kidney functions to balance T cell adhesion and migration

Mechanical Regulation of Cardiac Aging in Model Systems

Unlike diet and exercise, which individuals can modulate according to their lifestyle, aging is unavoidable. With normal or “healthy” aging, the heart undergoes extensive vascular, cellular, and interstitial molecular changes that result in stiffer less compliant hearts that experience a general decline in organ function. While these molecular changes deemed “cardiac remodeling” were once thought to be concomitant with advanced cardiovascular disease, they can be found in patients without manifestation of clinical disease. It is now mostly acknowledged that these age-related mechanical changes confer vulnerability of the heart to cardiovascular stresses associated with disease such as hypertension and atherosclerosis. However, recent studies have aimed at differentiating the initial compensatory changes that occur within the heart with age to maintain contractile function from the maladaptive responses associated with disease. This work has identified new targets to improve cardiac function during aging. Spanning invertebrate to vertebrate models, we use this review to delineate some hallmarks of physiological vs. pathological remodeling that occur in the cardiomyocyte and its microenvironment, focusing especially on the mechanical changes that occur within the sarcomere, intercalated disc, costamere, and extracellular matrix (ECM)