Prohibitins Are Required for Cancer Cell Proliferation and Adhesion

Prohibitin 1 (PHB1) is a highly conserved protein that together with its homologue prohibitin 2 (PHB2) mainly localizes to the inner mitochondrial membrane. Although it was originally identified by its ability to inhibit G1/S progression in human fibroblasts, its role as tumor suppressor is debated. To determine the function of prohibitins in maintaining cell homeostasis, we generated cancer cell lines expressing prohibitin-directed shRNAs. We show that prohibitin proteins are necessary for the proliferation of cancer cells. Down-regulation of prohibitin expression drastically reduced the rate of cell division. Furthermore, mitochondrial morphology was not affected, but loss of prohibitins did lead to the degradation of the fusion protein OPA1 and, in certain cancer cell lines, to a reduced capability to exhibit anchorage-independent growth. These cancer cells also exhibited reduced adhesion to the extracellular matrix. Taken together, these observations suggest prohibitins play a crucial role in adhesion processes in the cell and thereby sustaining cancer cell propagation and survival

Ca2+-activated Cl- currents are dispensable for olfaction

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Ca2+-activated Cl− currents are dispensable for olfaction

International audienceCanonical olfactory signal transduction involves the activation of cAMP-activated cation channels that depolarize the cilia of receptor neurons and raise intracellular calcium. Calcium then activates Cl- currents that may be up to 10-fold larger than cation currents and are believed to powerfully amplify the response. We now unambiguously identified Ano2 (Anoctamin2, TMEM16B) as the long-sought ciliary Ca++-activated Cl- channel of olfactory receptor neurons. Ano2 is expressed in the main olfactory epithelium (MOE) and in the vomeronasal organ (VNO) that additionally expresses the related Ano1 channel. Disruption of Ano2 in mice virtually abolished Ca++-activated Cl- currents in the MOE and VNO. Surprisingly, Ano2 disruption reduced fluid phase electroolfactogram responses by only ~40%, did not change air phase electroolfactograms, and did not reduce performance in olfactory behavioral tasks. In contrast to the current view, cyclic nucleotide-gated cation channels do not need a boost by Cl- channels to achieve near-physiological levels of olfaction