Abstract (eng)
The microtubule associated protein 1 S (MAP1S) is the shortest member of the mammalian MAP1 family of proteins. In contrast to MAP1A and MAP1B, which are predominantly expressed in the nervous system, MAP1S is expressed in a
wide range of tissues with the highest protein levels in brain and testis. All MAP1 proteins are synthesized as precursor proteins and then cleaved into a heavy and a light chain. MAP1S is partially cleaved in a tissue specific manner.
As light chains of MAP1 proteins bind to both, microtubules and filamentous actin, MAP1S (as all the other members of the family) might act as crosslinker protein between microtubules and actin filaments. Other potential interaction
partners of MAP1S (the testis-specific VCY2 protein, the fibroblast growth factor receptor associated protein LRPPRC, and the tumour suppressor protein RASSF1A) suggest functions of MAP1S in spermatogenesis, chromosome
remodelling, cytokinesis, apoptosis, and tumourigenesis.
In the first part of my thesis I looked at interactions between MAP1 proteins and posttranslational modifications of MAP1S in comparison to MAP1B and MAP1A. I found that all members of the MAP1 family can take part in heterotypic complexes formed between heavy and light chains probably via domains
conserved in all three MAP1 members. In contrast to MAP1B, the potential Snitrosylation of MAP1S does not influence its microtubule binding ability. Moreover, MAP1S, unlike MAP1B, is not modified by N-ε-lysine acetylation. In the second and major part of my thesis I investigated the role of MAP1S in
vivo by generating MAP1S deficient mice. Since MAP1S is ubiquitously expressed and might play a role in mitosis, I decided to generate conditional knockout mice to avoid the potential embryonic lethality of a homozygous MAP1S deletion. Surprisingly, I found that homozygous MAP1S knockout mice are viable and fertile and show no overt phenotype. Histological analysis showed no obvious abnormalities in brain or other organs, except for a
disturbed organisation of bile ducts in the liver in one MAP1S knockout mouse. Cultured MAP1S deficient primary neurons displayed a shift from one to two axons per cell body, indicating a role of MAP1S in neurotigenesis. Cultured fibroblasts revealed a crucial role of MAP1S in cell cycle progression and migration.