CLIP-associating protein (CLASP) 1 and CLASP2 are mammalian microtubule (MT) plus-end binding proteins, which associate with CLIP-170 and CLIP-115. Using RNA interference in HeLa cells, we show that the two CLASPs play redundant roles in regulating the density, length distribution and stability of interphase MTs. In HeLa cells, both CLASPs concentrate on the distal MT ends in a narrow region at the cell margin. CLASPs stabilize MTs by promoting pauses and restricting MT growth and shortening episodes to this peripheral cell region. We demonstrate that the middle part of CLASPs binds directly to EB1 and to MTs. Furthermore, we show that the association of CLASP2 with the cell cortex is MT independent and relies on its COOH-terminal domain. Both EB1- and cortex-binding domains of CLASP are required to promote MT stability. We propose that CLASPs can mediate interactions between MT plus ends and the cell cortex and act as local rescue factors, possibly through forming a complex with EB1 at MT tips.
Summary Humans and mice infected with different Plasmodium strains are known to produce microvesicles derived from the infected red blood cells (RBC), denoted RMVs. Studies in mice have shown that RMVs are elevated during infection and have pro-inflammatory activity. Here we present a detailed characterization of RMV composition and function in the human malaria parasite Plasmodium falciparum. Proteomics profiling revealed the enrichment of multiple host and parasite proteins, in particular of parasite antigens associated with host cell membranes and proteins involved in parasite invasion into RBCs. RMVs are quantitatively released during the asexual parasite cycle prior to parasite egress. RMVs demonstrate potent immunomodulatory properties on human primary macrophages and neutrophils. Additionally, RMVs are internalized by infected red blood cells and stimulate production of transmission stage parasites in a dose-dependent manner. Thus, RMVs mediate cellular communication within the parasite population and with the host innate immune system.
A study was made of the structure of the centrosome in the cell cycle in a nonsynchronous culture of pig kidney embryo (PE) cells. In the spindle pole of the metaphase cell there are two mutually perpendicular centrioles (mother and daughter) which differ in their ultrastructure . An electron-dense halo, which surrounds only the mother centriole and is the site where spindle microtubules converge, disappears at the end of telophase. In metaphase and anaphase, the mother centriole is situated perpendicular to the spindle axis . At the beginning of the G, period, pericentriolar satellites are formed on the mother centriole with microtubules attached to them ; the two centrioles diverge. The structures of the two centrioles differ throughout interphase ; the mother centriole has appendages, the daughter does not. Replication of the centrioles occurs approximately in the middle of the S period . The structure of the procentrioles differs sharply from that of the mature centriole. Elongation of procentrioles is completed in prometaphasé, and their structure undergoes a number of successive changes. In the G2 period, pericentriolar satellites disappear and some time later a fibrillar halo is formed on both mother centrioles, i .e ., spindle poles begin to form . In the cells that have left the mitotic cycle (Go period), replication of centrioles does not take place; in many cells, a cilium is formed on the mother centriole. In a small number of cells a cilium is formed in the S and G2 periods, but unlike the cilium in the Go period it does not reach the surface of the cell . In all cases, it locates on the centriole with appendages . At the beginning of the G, period, during the G2 period, and in nonciliated cells in the Go period, one of the centrioles is situated perpendicular to the substrate. On the whole, it takes a mature centriole a cycle and a half to form in PE cells.The behavior of centrioles in the cell cycle has been described in a number of works (13,21,22,24,29,30), but the majority of authors have confined themselves to a description of some individual cycle phases rather than making a comprehensive analysis of all the periods of interphase and mitosis . The emphasis in these works is on the location of centrioles in the cell and on the time of their duplication, whereas the interaction between interphase centrioles and cytoplasmic microtubules and the dynamics of all centrosome structures are hardly mentioned . Very little is known about the structure of the growing centriole in unciliated cells from the moment of its emergence near the mother centriole. Of great interest is the verification of the assumption about the oriented location of centrioles in mitosis and interphase.In the present work we have tried to elucidate the changes in centriole structure and general composition of the centriolar apparatus during and at completion of the mitotic cycle. The method was essentially as follows: we marked the individual cell under the light microscope and then examined the serial sections of this ...
BackgroundThe present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance.ResultsMPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform.ConclusionsImprovements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes.
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