Published online Apr 26, 2011. doi: 10.4331/wjbc.v2.i4.67
Revised: March 16, 2011
Accepted: March 23, 2011
Published online: April 26, 2011
Cells are equipped with mechanisms to control tightly the influx, efflux and resting level of free calcium (Ca2+). Inappropriate Ca2+ signaling and abnormal Ca2+ levels are involved in many clinical disorders including heart disease, Alzheimer’s disease and stroke. Ca2+ also plays a major role in cell growth, differentiation and motility; disturbances in these processes underlie cell transformation and the progression of cancer. Accordingly, research in the Strehler laboratory is focused on a better understanding of the molecular “toolkit” needed to ensure proper Ca2+ homeostasis in the cell, as well as on the mechanisms of localized Ca2+ signaling. A long-term focus has been on the plasma membrane calcium pumps (PMCAs), which are linked to multiple disorders including hearing loss, neurodegeneration, and heart disease. Our work over the past 20 years or more has revealed a surprising complexity of PMCA isoforms with different functional characteristics, regulation, and cellular localization. Emerging evidence shows how specific PMCAs contribute not only to setting basal intracellular Ca2+ levels, but also to local Ca2+ signaling and vectorial Ca2+ transport. A second major research area revolves around the calcium sensor protein calmodulin and an enigmatic calmodulin-like protein (CALML3) that is linked to epithelial differentiation. One of the cellular targets of CALML3 is the unconventional motor protein myosin-10, which raises new questions about the role of CALML3 and myosin-10 in cell adhesion and migration in normal cell differentiation and cancer.