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Significance of a novel WD-propeller-FYVE protein for signalling

English title Significance of a novel WD-propeller-FYVE protein for signalling
Applicant Mölling Karin
Number 116706
Funding scheme Project funding (Div. I-III)
Research institution Institut für Medizinische Virologie Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Biochemistry
Start/End 01.04.2007 - 31.12.2008
Approved amount 129'975.00
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Keywords (6)

WD-repeats; FYVE domain; akt; PKCzeta/lambda; insulin; vesicular associated membrane protein 2

Lay Summary (English)

Lead
Lay summary
We have identified a new protein, a propeller protein, which plays a role in insulin metabolism. The propeller protein is present in specialized fat cells, adipocytes, and muscle cells, which respond to insulin stimulation. When these cells are treated with insulin in cell culture, the propeller protein recruits other cellular proteins to form a larger complex. These proteins comprise two kinases, Akt and a PKC-subtype, which bind preferentially after insulin stimulation. The propeller also recruits cellular substrates, which are then brought into proximity of the kinases by the propeller and become phosphorylated in response to insulin. This sets into motion an intracellular signalling process, transmitting information to the membrane as well as to the nucleus. The complex travels to the membrane, where it binds to a docking protein, VAMP2, leading to changes in glucose transport through the membrane. We want to understand the steps involved in this process and the consequences of the insulin stimulation on glucose uptake. Also the nucleus undergoes changes by the insulin-mediated signal cascade. A nuclear regulator, Foxo1, is shut down, which allows new protein expression. We are interested in analyzing the nuclear events and the newly expressed proteins. They will be studied in adipocytes, while they undergo a differentiation process. One of the adipocyte-specific marker proteins is called PPARgamma, which we will analyze. The fat droplets in these cells can be stained by a red dye and are visible by eye as indicator of specialization of the cells.Thus, the propeller protein with its associated components is an essential link between insulin and glucose metabolism. It is also involved in regulation of gene expression. Our studies may have implications for insulin-dependent human diseases such as obesity or diabetes II. We may have identified a new target interesting for therapeutic intervention.
Direct link to Lay Summary Last update: 21.02.2013

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