Fayal Abderemane-Ali, PhD, UCSF, San Francisco, USA

Ion channel modulation by calmodulin: a view of the starting and ending points

Voltage-gated ion channels (VGIC) are multi-subunit membrane proteins that respond to changes in membrane potential with conformational changes that lead to opening or closing of an ion-selective pore. The passage of ions through these channels produces the bioelectricity responsible for the generation and propagation of action potentials in electrically excitable cells. Auxiliary subunits associate with these VGIC to form macromolecular complexes and regulate channel activity, ensuring a proper excitability in various organs such as the heart, brain and skeletal muscles. One of the most important auxiliary subunits is calmodulin (CaM), a Ca²⁺-sensor protein that can adopt different conformations depending on the level of Ca²⁺, leading to a Ca²⁺-dependent regulation of its targets. The importance of CaM in VGIC regulation has been extensively investigated by numerous studies. Recently, we uncovered the molecular mechanisms by which CaM initiates the Ca²⁺-dependent modulation of a family of VGIC named Kv7 (or KCNQ). On an even more recent study, we also established the ending point of CaM regulation on another family of VGIC named Cav. This second study led to the discovery of a new gate in these Cav channels. During this seminar, I will present the results, implications and future directions from these two major studies exhibiting a molecular view of the starting and ending points of ion channel modulation by CaM.

BIOGRAPHY

Dr. Fayal Abderemane-Ali is an American Heart Association postdoctoral fellow at the Cardiovascular Research Institute of the University of California San Francisco (UCSF) since 2014.

Fayal completed his PhD in Electrophysiology and Ion channel Biophysics at l’institut du thorax in 2013 under Dr. Gildas Loussouarn’s mentorship. During his PhD training, Fayal was granted a Fulbright fellowship to spend a year in the laboratory of Pr. Daniel Minor at UCSF where he is currently using both functional and structural approaches to uncover how ion channels work, and the molecular mechanisms by which poisonous organisms resist toxins that target ion channels.