of the Max - MDC

Structure of the Group
Group Leader
Prof. Dr. Michael Gotthardt
Scientists
Dr. Agnieszka Pietas
Dr. Yu Shi
Dr. Michael Radke
Dr. Katy Raddatz
Graduate and Undergraduate
Students
Stefanie Weinert*
Chen Chen*
Uta Wrackmeyer*
Ulrike Lisewski*
Thirupugal Govindarajan*
Technical Assistants
Beate Goldbrich
Regina Pieske**
Mandy Terne**
* part of the period reported
** guest, part of the period reported
Schematic diagram of the sarcomere. Titin forms a continous filament system along the muscle fiber overlapping
in the M-band (titin C-terminus) and in the Z-disc (N-terminus). The titin kinase is found near the
edge of the M-band region, while the elastic PEVK resides in the I-band. Titin interacts with a plethora of sarcomeric
proteins, such as T-cap and C-protein.
Functional analysis of the Coxsackie-Adenovirus
Receptor
Yu Shi, Chen Chen, Uta Wrackmeyer, Ulrike Lisewski
CAR was cloned as a receptor used by adeno- and coxsackievirus
to enter cells but its physiological role has remained
obscure. Detailed information on the expression pattern
such as upregulation surrounding myocardial infarction and
a critical role in embryonic development (lethality in midgestation
of the CAR knockout) are well established, but no
information on its role in the adult heart has been available.
We have generated both tissue culture and animal models to
study CAR’s function in cardiac remodeling, inflammatory
cardiomyopathy, and basic cellular processes such as endocytosis
and cell-cell contact formation.
Our preliminary data suggest a critical role of CAR in the
conduction of electrical signals from the atria to the cardiac
ventricle. The inducible heart-specific knockout of CAR has
enabled us to completely block the entry of coxsackievirus
into cardiomyocytes and prevent all signs of inflammatory
cardiomyopathy.
Selected Publications
Granzier HL, Radke M, Royal J, Wu Y, Irving TC, Gotthardt M,
Labeit S. (2007) Functional genomics of chicken, mouse, and
human titin supports splice diversity as an important mechanism
for regulating biomechanics of striated muscle. Am J
Physiol Regul Integr Comp Physiol. 293(2): R557-67
Radke, M, Peng, J, Wu, Y, McNabb, M, Nelson, OL, Granzier, H,
Gotthardt, M. (2007) Targeted deletion of Titin’s N2B region
leads to diastolic dysfunction and cardiac atrophy. Proc. Natl.
Acad. Sci. USA. 104(9), 3444-3449
Peng J, Raddatz, K, Molkentin, JD, Wu, Y, Labeit, S, Granzier, H,
Gotthardt, M. (2007) Cardiac hypertrophy and reduced contractility
in titin kinase deficient hearts. Circulation 13;115(6):
743-5
Weinert, S, Bergmann, N, Luo, X, Erdmann, B, Gotthardt, M.
(2006). Muscle atrophy in Titin M-line deficient mice. Journal of
Cell Biology 173(4), 559-570
Peng, J, Raddatz, K, Labeit, S, Granzier, H, Gotthardt, M.
(2006). Muscle atrophy in Titin M-line deficient mice. J Muscle
Res and Cell Motility 10,1-8
Andersen, OA, Reiche, J, Schmidt, V, Gotthardt, M, Spoelgen, R,
Behlke, J, von Arnim, CA F, Breiderhoff, T, Jansen, P, Wu, X,
Bales, KR, Cappai, R, Masters, CL, Gliemann, J, Mufson, EJ,
Hyman, BT, Paul, SM, Nykjær, N and T E Willnow. (2005)
SorLA/LR11, a neuronal sorting receptor that regulates processing
of the amyloid precursor protein. Proc. Natl. Acad. Sci. USA.
102(38), 13461-6
Cardiovascular and Metabolic Disease Research 47