High impact information on Pcnt

• Pericentrin, a highly conserved centrosome protein involved in microtubule organization [1].
• These results suggest that pericentrin is a conserved integral component of the filamentous matrix of the centrosome involved in the initial establishment of organized microtubule arrays [1].
• Antisera recognize a 220 kd protein and stain centrosomes and acentriolar microtubule-organizing centers, where the protein is localized to the pericentriolar material (hence, the name pericentrin) [1].
• Pcnt is found in spermatocyte IFT fractions, and IFT proteins are found in isolated centrosome fractions [2].
• Pcnt antibodies coimmunoprecipitate IFT proteins and PC2 from several cell lines and tissues [2].

Biological context of Pcnt

• However, comparison of the published mouse pericentrin cDNA sequence to mouse genomic DNA sequences revealed two important differences: the stop codon present in the published mouse pericentrin cDNA is not found in the mouse genomic sequence, and the 3' end of the published mouse pericentrin cDNA is a fragment from a different mouse chromosome [3].
• To resolve these discrepancies, we sequenced a mouse expressed sequence tag (EST) that corresponds to the 3' end for a 7.1-kb mouse pericentrin RNA encoded on chromosome 10 [3].
• No candidate hereditary disorder for pericentrin deficiency/abnormality has yet been mapped in the most distal region of 21q; in addition the role of triplication of the pericentrin gene in the pathophysiology or etiology of trisomy 21 is currently unknown [4].
• Spindles in pericentrin-overexpressing cells were disorganized and mispositioned, and chromosomes were misaligned and missegregated during cell division, giving rise to aneuploid cells [5].
• The metaphase spindle at meiosis-II had incomplete pericentrin rings at both spindle poles [6].

Anatomical context of Pcnt

• Here, we show that the centrosome protein pericentrin (Pcnt) colocalizes with IFT proteins to the base of primary and motile cilia [2].
• Pericentrin (Pcnt) is a giant coiled-coil protein known to mediate microtubule organization [7].
• Furthermore, IVO oocytes showed a twofold increase in cytoplasmic microtubule organizing centers (MTOCs), and constitutive MTOC proteins (gamma-tubulin and pericentrin) were excluded from the first polar body [8].
• Centrosomal deployment of gamma-tubulin and pericentrin: evidence for a microtubule-nucleating domain and a minus-end docking domain in certain mouse epithelial cells [9].
• After expression of a GFP-tagged gammatub, we observe a weak fluorescence along the nuclear membrane, confirming the presence of gammatub at a low concentration relative to PC [10].

Associations of Pcnt with chemical compounds

• Treatment of cells with 0.5 M NaCl dissociates gamma-tubulin from the centrosome and disrupts the association of phosphoinositide 3-kinase with pericentrin, but not gamma-tubulin [11].
• Vanadate treatment, a known inhibitor of dynein-ATPase, resulted in meiotic arrest, constriction of the spindle pole, and an aggregation of pericentrin at the spindle poles [6].
• To investigate these questions, we have examined the redistribution of the centrosomal proteins pericentrin (PC), gammatub, and ninein in the C2 muscle cell line [10].
• To test which of the above mechanisms or combination of mechanisms are responsible we investigated the re-formation of microtubules after depolymerisation by nocodazole, using antibodies against pericentrin, gamma-tubulin, EB1, and tyrosinated alpha-tubulin [12].

Physical interactions of Pcnt

• We conclude that pericentrin forms complexes with CHD3 and CHD4, but a distinct CHD3-pericentrin complex is required for centrosomal anchoring of pericentrin/gamma-tubulin and for centrosome integrity [13].

Other interactions of Pcnt

• Like pericentrin, p-MARCKS staining at the MI spindle poles was asymmetric [14].
• To define the basis for this interaction, pericentrin was coexpressed with cytoplasmic dynein heavy (DHCs), intermediate (DICs), and light intermediate (LICs) chains, and the dynamitin and p150(Glued) subunits of dynactin [5].

Analytical, diagnostic and therapeutic context of Pcnt

• Immunogold electron microscopy demonstrates that Pcnt is on or near basal bodies at the base of cilia [2].
• Immunofluorescence analysis confirmed preferential expression of the Pcnt protein in G(0) phase cells [7].
• In situ hybridization analysis revealed preferential expression of Pcnt in quiescent G(0) phase cells throughout the embryo with an unexpectedly low expression level in proliferating cells, suggesting that Pcnt might not play an important role in mitotic proliferation [7].
• Extensive northern blot analysis revealed that the pericentrin gene displays a complex expression pattern in both mouse and human: a 10-kb kendrin transcript is found in most tissues, whereas smaller transcripts are detected in a limited subset of tissues [3].
• Immunoprecipitation of endogenous pericentrin also pulled down cytoplasmic dynein in untransfected cells [5].

References