TY  - JOUR
A1  - Gehmlich, Katja
A1  - Geier, C.
A1  - Osterziel, Karl Joseph
A1  - Fürst, Dieter Oswald
T1  - Mutant muscle LIM protein is associated with hypertrophic cardiomyopathy and exhibits altered binding properties in the system MLP - N-RAP - alpha-actinin
Y1  - 2004
SN  - 0171-9335
ER  - 
TY  - JOUR
A1  - Gehmlich, Katja
A1  - Geier, C.
A1  - Osterziel, Karl Joseph
A1  - VanderVen, Peter F. M.
A1  - Fürst, Dieter Oswald
T1  - Decreased interactions of mutant muscle LIM protein (MLP) with N-RAP and alpha-actinin and their implication for hypertrophic cardiomyopathy
N2  - Previous work has shown that mutations in muscle LIM protein (MLP) can cause hypertrophic cardiomyopathy (HCM). In order to gain an insight into the molecular basis of the disease phenotype, we analysed the binding characteristics of wild-type MLP and of the (C58G) mutant MLP that causes hypertrophic cardiomyopathy. We show that MLP can form a ternary complex with two of its previously documented myofibrillar ligand proteins, N-RAP and alpha-actinin, which indicates the presence of distinct, non-overlapping binding sites. Our data also show that, in comparison to wild-type MLP, the capacity of the mutated MLP protein to bind both N-RAP and alpha-actinin is significantly decreased. In addition, this single point mutation prevents zinc coordination and proper folding of the second zinc-finger in the first LIM domain, which consequently renders the protein less stable and more susceptible to proteolysis. The molecular basis for HCM-causing mutations in the MLP gene might therefore be an alteration in the equilibrium of interactions of the ternary complex MLP-N-RAP-alpha-actinin. This assumption is supported by the previous observation that in the pathological situation accompanied by MLP down regulation, cardiomyocytes try to compensate for the decreased stability of MLP protein by increasing the expression of its ligand N-RAP, which might finally result in the development of myocyte disarray that is characteristic of this disease
Y1  - 2004
SN  - 0302-766X
ER  - 
TY  - JOUR
A1  - Gehmlich, Katja
A1  - Hayess, Katrin
A1  - Legler, Christof
A1  - Haebel, Sophie
A1  - van der Ven, Peter F. M.
A1  - Ehler, Elisabeth
A1  - Fuerst, Dieter O.
T1  - Ponsin interacts with Nck adapter proteins : implications for a role in cytoskeletal remodelling during differentiation of skeletal muscle cells
N2  - Skeletal muscle differentiation is a complex process: It is characterised by changes in gene expression and protein composition. Simultaneously, a dramatic remodelling of the cytoskeleton and associated cell-matrix contacts, the costameres, occurs. The expression and localisation of the protein ponsin at cell-matrix contacts marks the establishment of costameres. In this report we show that skeletal muscle cells are characterised by a novel ponsin isoform, which contains a large insertion in its carboxy-terminus. This skeletal muscle-specific module binds the adapter proteins Nck1 and Nck2, and increased co-localisation of ponsin with Nck2 is observed at remodelling cell-matrix contacts of differentiating skeletal muscle cells. Since this ponsin insertion can be phosphorylated, it may adjust the interaction affinity with Nck adapter proteins. The novel ponsin isoform and its interaction with Nck1/2 provide exciting insight into the convergence of signalling pathways at the costameres, and its crucial role for skeletal muscle differentiation and re-generation.
Y1  - 2010
UR  - http://www.sciencedirect.com/science/journal/01719335
U6  - https://doi.org/10.1016/j.ejcb.2009.10.019
SN  - 0171-9335
ER  -