Functional characterization of the novel centrosomal protein Nlp (ninein-like protein)

摘要: The centrosome is the major microtubule organizing centre (MTOC) in animal cells. Most microtubules (MTs) emanate from centrosome, where gamma-tubulin ring complexes (gammaTuRCs) act as templates for MT nucleation. During interphase, organizes a array that imparts shape and polarity to cell essential intracellular transport positioning of organelles such Golgi apparatus. mitosis, centrosomes ensure bipolarity correct orientation spindle by forming poles. In order switch interphasic mitotic state, undergoes structural reorganization, termed maturation, which mainly characterized an increase nucleation activity. A full appreciation how contribute cellular functions requires isolation characterization unknown centrosome-associated molecules. Here we describe identification novel centrosomal component, human protein Nlp (ninein-like protein) related previously MT-anchoring ninein. In first part present thesis substrate Polo-like kinase 1 (Plk1), important regulator mitosis whose activity required maturation. interacts with two distinct gammaTuRC components, hGCP4, stimulates Plk1 phosphorylates disrupts its association. Overexpression mutant lacking phosphorylation sites induces defects formation. We propose acts binding (GTBP), contributing during interphase. At onset displacement triggered could represent step maturation process allows state. Thus, conclude Nlp, well ninein, plays role organization. However function these proteins possibly diverged evolution: whilst gained more prominent nucleation, ninein became principally involved anchoring. In second this report initial molecular mechanisms underlying ability induce fragmentation apparatus when overexpressed show affect organization clearly depends on their capacity associate cytoplasmic dynein-dynactin complex, motor complex primarly maintainance architecture. excess disruption sequestering complexes. Future investigations should be aimed at understanding whether dissociation induced interfere migration polarization processes, require highly coordinated action organelles. Cell critical events immune responses embryonic development, invasive growth metastasis. Thus, our findings raise interesting possibility upregulation expression levels basis developmental disorders malfunctioning system and, other hand, modulate acquisition properties neoplastic