Research
Group Schwaller
Calcium-binding proteins
as essential components
in the regulation
of intracellular Ca2+ homeostasis
Project description
Together with the ubiquitous calmodulin, the EF-hand containing calcium-binding proteins parvalbumin (PV), calbindin D-28k (CB) and calretinin (CR) are the most abundantly expressed members of this family in the brain. Formerly, they were classified as simple buffers serving to “clamp” the intracellular calcium concentration [Ca2+]i. But recent studies regularly using transgenic mice have revealed these molecules to play pivotal roles in Ca2+ homeostasis and signaling. The three proteins are important for synaptic plasticity and related rhythmic activities within neuronal networks. The lack of any of these proteins in knockout mice induces specific compensation mechanisms including changes in cell morphology and organelle biosynthesis. Furthermore, CR is a specific marker for mesotheliomas, a tumor derived from the lining of the body cavity (peritoneum), and CR expression is also observed in a majority of poorly differentiated colon tumors.
We are interested in the specific functions of the three proteins PV, CR and CB in all the organs where they are expressed. All three are found in subpopulations of nerve cells, PV also in fast-twitch muscles. In the distal nephron of the kidney CB and PV are implicated in the fine-tuning of Ca2+ resorption.
As research models, we use transgenic mice deficient for these three CaBPs and mice ectopically expressing PV in the brain. These animals are used to detect changes at the level of I) morphology (e.g. light (confocal)- and electron microscopy), II) molecules implicated in Ca2+ homeostasis (RT-PCR, Western blots, ELISA, immunohistochemistry) and III) organ function (muscle, kidney, brain). We also perform tests to define the behavioral phenotype of mice deficient for either one or combinations of these CaBPs. For the projects related to tumor biology we work with cell culture models of mesotheliomas and colon cancer.
Group members
Martine Steinauer (technician), Valérie Salicio (technician), Nadège Fahrni (technician), Lenke Horvath (PhD student), Walter Blum (PhD student), Thomas Henzi (PhD, postdoc), Laszlo Pecze (PhD, postdoc), Beat Schwaller (PhD, group leader, associate professsor).
Funding
Swiss National Science Foundation; intramural budget (University of Fribourg).
