Novel asymmetrically localizing components of human centrosomes identified by complementary proteomics methods.

Centrosomes in animal cells are dynamic organelles with a proteinaceous matrix of pericentriolar material assembled around a pair of centrioles. They organize the microtubule cytoskeleton and the mitotic spindle apparatus. Mature centrioles are essential for biogenesis of primary cilia that mediate key signalling events.

Plk4 trans-autophosphorylation regulates centriole number by controlling betaTrCP-mediated degradation.

Centrioles are the main constituents of the mammalian centrosome and act as basal bodies for ciliogenesis. Centrosomes organize the cytoplasmic microtubule network during interphase and the mitotic spindle during mitosis, and aberrations in centrosome number have been implicated in chromosomal instability and tumor formation. The centriolar protein Polo-like kinase 4 (Plk4) is a key regulator of centriole biogenesis and is crucial for maintaining constant centriole number, but the mechanisms regulating its activity and expression are only beginning to emerge.

Control of centriole length by CPAP and CP110.

Centrioles function as the major components of centrosomes, which organize microtubule (MT) arrays in proliferating cells, and as basal bodies for primary cilia formation in quiescent cells. Centrioles and basal bodies are structurally similar, barrel-shaped organelles composed of MTs. In proliferating cells, two new centrioles, termed procentrioles, form during the S phase of the cell cycle in close proximity to the proximal ends of the two preexisting parental centrioles, often at a near-orthogonal angle.

Differential role of reactive oxygen species in the activation of mitogen-activated protein kinases and Akt by key receptors on B-lymphocytes: CD40, the B cell antigen receptor, and CXCR4.

Background: Antibodies produced by B-lymphocytes play a key role in the host defense against infection. The development, survival, and activation of B cell is regulated by multiple receptors including the B cell antigen receptor (BCR), which detects the presence of pathogens, CD40, which binds co-stimulatory molecules on activated T cells, and chemokines such as SDF-1 (CXCL12) that play key roles in B cell development and trafficking. Signaling by many receptors results in the generation of reactive oxygen species (ROS) that function as second messengers by regulating the activity of redox-sensitive kinases and phosphatases.

Plk4-induced centriole biogenesis in human cells.

We show that overexpression of Polo-like kinase 4 (Plk4) in human cells induces centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole. This provided an opportunity for dissecting centriole assembly and characterizing assembly intermediates. Critical components were identified and ordered into an assembly pathway through siRNA and localized through immunoelectron microscopy.

The Rap GTPases mediate CXCL13- and sphingosine1-phosphate-induced chemotaxis, adhesion, and Pyk2 tyrosine phosphorylation in B lymphocytes.

The localization of B cells to lymphoid organs where they can become activated and differentiate into antibody-secreting plasma cells is controlled by multiple chemoattractants that promote cell migration and integrin-mediated adhesion. CXCL13 and sphingosine 1-phosphate (S1P) are two important chemoattractants that control the trafficking of B cells. CXCL13 directs B lymphocytes to lymphoid follicles where they receive survival signals and, if activated, undergo a germinal center response.