Endocytosis, a process of plasma membrane invaginations, is a fundamental cellular mechanism, ensuring uptake of nutrients, enhanced communication between cells, protective functions against invasive pathogens and remodelling of the plasma membrane composition. In turn, endocytic mechanisms are exploited by pathogens to enter their host cells. Endocytosis comprises multiple forms of which our molecular understanding has mostly advanced with respect to clathrin-mediated endocytosis and phagocytosis. Studies on the small GTPase Rab5 have provided important insights into the molecular mechanism of endocytosis and transport in the early stages of the endocytic pathways. Rab5 is a key regulator of clathrin-mediated endocytosis, but in addition, localises to several distinct endocytic carriers including phagosomes and pinocytic vesicles. On early endosomes, Rab5 coordinates within a spatially restricted domain enriched in phosphatidylinositol-3 phosphate PI(3)P a complex network of effectors, including PI3-Kinase (PI3-K), the FYVE-finger proteins EEA1 and Rabenosyn-5 that functionally cooperate in membrane transport. Moreover, Rab5 regulates endocytosis from the apical and basolateral plasma membrane in polarised epithelial cells. During my PhD thesis, I investigated the molecular mechanisms of endocytosis both in polarised and non-polarised cells. I obtained new insights into the molecular mechanisms of endocytosis and their coordination through the functional characterization of a novel Rab5 effector, termed Rabankyrin-5. I could demonstrated that Rabankyrin-5 is a novel PI(3)P-binding Rab5 effector that localises to early endosomes and stimulates their fusion activity in vitro. The latter activity depends on the oligomerisation of Rabankyrin-5 on the endosomal membrane via the N-terminal BTB/POZ domain. In addition to early endosomes, however, Rabankyrin-5 localises to large vacuolar structures that correspond to macropinosomes in epithelial cells and fibroblasts. Overexpression of Rabankyrin-5 increases the number of macropinosomes and stimulates fluid phase uptake whereas its downregulation through RNA interference inhibits these processes. In polarised epithelial cells, the function of Rabankyrin-5 is primarily restricted to the apical membrane. It localises to large pinocytic structures underneath the apical surface of kidney proximal tubule cells and its overexpression in polarised MDCK cells specifically stimulates apical but not basolateral, non-clathrin mediated pinocytosis. In demonstrating a regulatory role in endosome fusion and (macro)-pinocytosis, my studies suggest that Rab5 regulates and coordinates different endocytic mechanisms through its effector Rabankyrin-5. Furthermore, the active role in apical pinocytosis in epithelial cells suggests an important function of Rabankyrin-5 in the physiology of polarised cells. The results obtained in this thesis are central not only for our understanding of the basic principles underlying the regulation of multiple endocytic mechanisms. They are also relevant for the biomedical field, since actin-dependent (macro)-pinocytosis is an important mechanism for the physiology of cells and organisms and is upregulated under certain pathological conditions (e.g. cancer).

This thesis examines the relationship between the Communist Party of India (Marxist)-led Left Front Government and the media in the provincial state of West Bengal, India, during the thirty four years (1977-2011) period when the party was in government. The main aim of the thesis is to investigate the relation between the CPI (M) led Left Front Government and the media in West Bengal (1977-2011), the role of the media in stabilising or destabilising the Left Front Government, the impact of neoliberalism on the Left Front Government and their relation with the media, the role of the media in communicating developmental policies of the LFG to the public and finally the role which the mainstream and the party controlled media played in the public sphere. These questions are addressed through document research of CPI (M)’s congress and conference reports, manifestos, press releases, pamphlets, leaflets, booklets; and interviews with the CPI (M) leadership and the Editors and Bureau Chiefs of the key newspapers and television channels in West Bengal. The findings are contextualised within a broader discussion of the political and historical transitions India and West Bengal have gone through in this period (chapter 4). This is the first study looking at the relationship between the media and the CPI (M) led Left Front Government over a period of thirty four years (1977-2011). The thesis finds that neoliberalism in India had considerable effects on the CPI (M), the media and their relationship. The research finds a continuous effort from the mainstream and the party-controlled media to dominate the public sphere leading debates in order to seek some form of political consensus in order to govern. The media in West Bengal were politically divided between the left and the opposition. The research finds that this generated a market for political advertisements and political news contributing to a politically polarised media market in West Bengal that assisted in generating revenue for the media. The findings also suggest that the media contributed to rather than played a determining role in destabilising the Left Front Government. Finally the research finds that the CPI (M) had an arduous relation with the media since 1977 when the party decided to participate in the parliamentary democracy. The LFG and the mainstream media entered into an antagonistic relationship post 1991 contributing to a politically polarised media market in West Bengal.