Expression of TAU in insulin-secreting cells and its interaction with the calcium-binding protein secretagogin

Maj, Magdalena and Gartner, Wolfgang and Ilhan, Aysegul and Neziri, Dashurie and Attems, Johannes and Wagner, Ludwig (2010) Expression of TAU in insulin-secreting cells and its interaction with the calcium-binding protein secretagogin. Journal of Endocrinology, 205. pp. 25-36.

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Tauopathies have been associated with Alzheimer’s disease
(AD), which frequently manifests together with diabetes
mellitus type 2. Calcium-binding proteins such as the recently
identified secretagogin (SCGN) might exert protective
effects. As pancreatic b-cells and neurons share common
electrophysiological properties, we investigated the appearance
of TAU (listed as MAPT in the HUGO and MGI
Databases) protein at the islets of Langerhans and b-cellderived
cell lines which highly express the neuroendocrinespecific
protein SCGN. Six predominant TAU isoforms
could be identified by immunoblotting, which formed TAU
deposits detectable by immunofluorescence and sarkosylinsoluble
pellets. Using GST–SCGN pull-down assays, a
calcium-dependent SCGN–TAU interaction was found. In
this line, sucrose density gradient fractionation and differential
ultracentrifugation studies of TAU and SCGN revealed
co-appearance of both proteins. Co-localization of TAU
and SCGN within insulinoma cells and islets of Langerhans
mainly restricted to insulin-positive b-cells was demonstrated
by confocal microscopy. Motivated by these findings, we
looked if SCGN overexpression could exert protective
function on Rin-5F cells, which showed differences in
TAU levels. Testing the vulnerability of Rin-5F clones by
MTT assay, we revealed that high TAU levels going along
with highest TAU aggregates could not be antagonized by
high levels of SCGN protein. Our findings demonstrated for
the first time the association of TAU and the calcium-binding
protein SCGN and support earlier results implicating that
b-cells might represent an extra cerebral site of tauopathy

Item Type: Article
Subjects: Medical and Health Sciences > Basic medicine
Medical and Health Sciences > Clinical medicine
Medical and Health Sciences > Other medical sciences
Divisions: Faculty of Medical Science
Depositing User: Biljana Kosturanova
Date Deposited: 05 Mar 2013 15:27
Last Modified: 05 Mar 2013 15:27

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