Cep215 is essential for morphological differentiation of astrocytes

Abstract Cep215 (also known as Cdk5rap2) is a centrosome protein which is involved in microtubule organization. Cep215 is also placed at specific subcellular locations and organizes microtubules outside the centrosome. Here, we report that Cep215 is involved in morphological differentiation of astrocytes. Cep215 was specifically localized at the glial processes as well as centrosomes in developing astrocytes. Morphological differentiation of astrocytes was suppressed in the Cep215-deleted P19 cells and in the Cep215-depleted embryonic hippocampal culture. We confirm that the microtubule organizing function of Cep215 is critical for the glial process formation. However, Cep215 is not involved in the regulation of cell proliferation nor cell specification. Based on the results, we propose that Cep215 organizes microtubules for glial process formation during astrocyte differentiation.

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The role of cAMP in nerve growth factor-promoted neurite outgrowth in PC12 cells.

The Journal of Cell Biology ◽

10.1083/jcb.102.3.821 ◽

1986 ◽

Vol 102 (3) ◽

pp. 821-829 ◽

Cited By ~ 122

Author(s):

C Richter-Landsberg ◽

B Jastorff

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Neurite Outgrowth ◽

Pc12 Cells ◽

Morphological Differentiation ◽

Intracellular Camp ◽

Nerve Growth ◽

Process Formation ◽

Dependent Protein

Nerve growth factor (NGF)-mediated neurite outgrowth in rat pheochromocytoma PC12 cells has been described to be synergistically potentiated by the simultaneous addition of dibutyryl cAMP. To elucidate further the role of cAMP in NGF-induced neurite outgrowth we have used the adenylate cyclase activator forskolin, cAMP, and a set of chemically modified cAMP analogues, including the adenosine cyclic 3',5'-phosphorothioates (cAMPS) (Rp)-cAMPS and (Sp)-cAMPS. These diastereomers have differential effects on the activation of cAMP-dependent protein kinases, i.e., (Sp)-cAMPS behaves as a cAMP agonist and (Rp)-cAMPS behaves as a cAMP antagonist. Our data show that the establishment of a neuritic network, as observed from PC12 cells treated with NGF alone, could not be induced by either forskolin, cAMP, or cAMP analogues alone. The presence of NGF in combination with forskolin or cAMP or its agonistic analogues potentiated the initiation of neurite outgrowth from PC12 cells. The (Sp)-cAMPS-induced stimulation of NGF-mediated process formation was successfully blocked by the (Rp)-cAMPS diastereomer. On the other hand, NGF-stimulated neurite outgrowth was not inhibited by the presence of the cAMP antagonist (Rp)-cAMPS. We conclude that the morphological differentiation of PC12 cells stimulated by NGF does not require cAMP as a second messenger. The constant increase of intracellular cAMP, caused by either forskolin or cAMP and the analogues, in combination with NGF, not only rapidly stimulated early neurite outgrowth but also exerted a maintaining effect on the neuronal network established by NGF.

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Morphological Differentiation of Oligodendrocytes Requires Activation of Fyn Tyrosine Kinase

The Journal of Cell Biology ◽

10.1083/jcb.145.6.1209 ◽

1999 ◽

Vol 145 (6) ◽

pp. 1209-1218 ◽

Cited By ~ 149

Author(s):

Donna J. Osterhout ◽

Amy Wolven ◽

Rebecca M. Wolf ◽

Marilyn D. Resh ◽

Moses V. Chao

Keyword(s):

Tyrosine Kinase ◽

Kinase Activity ◽

Kinase Inhibitors ◽

Morphological Differentiation ◽

Dominant Negative ◽

Tyrosine Kinase Activity ◽

Oligodendrocyte Progenitors ◽

Differentiated Cells ◽

Process Formation ◽

Fyn Tyrosine Kinase

In the central nervous system, myelination of axons occurs when oligodendrocyte progenitors undergo terminal differentiation and initiate process formation and axonal ensheathment. Although it is hypothesized that neuron-oligodendrocyte contact initiates this process, the molecular signals are not known. Here we find that Fyn tyrosine kinase activity is upregulated very early during oligodendrocyte progenitor cell differentiation. Concomitant with this increase is the appearance of several tyrosine phosphorylated proteins present only in differentiated cells. The increased tyrosine kinase activity is specific to Fyn, as other Src family members are not active in oligodendrocytes. To investigate the function of Fyn activation on differentiation, we used Src family tyrosine kinase inhibitors, PP1 and PP2, in cultures of differentiating oligodendrocyte progenitors. Treatment of progenitors with these compounds prevented activation of Fyn and reduced process extension and myelin membrane formation. This inhibition was reversible and not observed with related inactive analogues. A similar effect was observed when a dominant negative Fyn was introduced in progenitor cells. These findings strongly suggest that activation of Fyn is an essential signaling component for the morphological differentiation of oligodendrocytes.

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From tip to toe – dressing centrioles in γTuRC

Journal of Cell Science ◽

10.1242/jcs.258397 ◽

2021 ◽

Vol 134 (14) ◽

Author(s):

Nina Schweizer ◽

Jens Lüders

Keyword(s):

Cell Proliferation ◽

Proximal Part ◽

Supporting Cell ◽

Canonical Function ◽

Microtubule Organization ◽

Classical View ◽

Cylindrical Structures ◽

Ring Complex ◽

Pericentriolar Material ◽

And Function

ABSTRACT Centrioles are microtubule-based cylindrical structures that assemble the centrosome and template the formation of cilia. The proximal part of centrioles is associated with the pericentriolar material, a protein scaffold from which microtubules are nucleated. This activity is mediated by the γ-tubulin ring complex (γTuRC) whose central role in centrosomal microtubule organization has been recognized for decades. However, accumulating evidence suggests that γTuRC activity at this organelle is neither restricted to the pericentriolar material nor limited to microtubule nucleation. Instead, γTuRC is found along the entire centriole cylinder, at subdistal appendages, and inside the centriole lumen, where its canonical function as a microtubule nucleator might be supplemented or replaced by a function in microtubule anchoring and centriole stabilization, respectively. In this Opinion, we discuss recent insights into the expanded repertoire of γTuRC activities at centrioles and how distinct subpopulations of γTuRC might act in concert to ensure centrosome and cilia biogenesis and function, ultimately supporting cell proliferation, differentiation and homeostasis. We propose that the classical view of centrosomal γTuRC as a pericentriolar material-associated microtubule nucleator needs to be revised.

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Cell proliferation during morphogenetic change; analysis of frontonasal morphogenesis in the chick embryo employing DNA labeling indices

Development ◽

10.1242/dev.40.1.101 ◽

1977 ◽

Vol 40 (1) ◽

pp. 101-113

Author(s):

Robert Minkoff ◽

Amy J. Kuntz

Keyword(s):

Cell Proliferation ◽

Chick Embryo ◽

Developmental Stages ◽

Change Analysis ◽

Dna Labeling ◽

Process Formation ◽

Nasal Process ◽

Primary Palate ◽

Early Primary

The role of cell proliferation was analyzed in the chick embryo system employing DNA labeling indices during the invagination of the olfactory placode and the development of the lateral and medial nasal processes. Chick embryos were labeled for 1 h with [3H]thymidine and processed histologically and autoradiographically. The percentage of labeled mesenchymal cells in delineated areas within and adjacent to the nasal processes was determined. From analysis of labeling indices of each area at successive developmental stages, it was concluded that cell proliferation of mesenchyme, as measured by DNA labeling indices, did not appear to increase during the formation of the nasal processes, and that cell proliferation actually declined during the later stages of nasal process formation. Differences were also found between the labeling indices of the mesenchyme of the nasal processes as compared to that of adjacent areas. These differences tended to become greater as development progressed. In all of the areas studied, cell proliferation declined during the later stages of development but the magnitude of the decline was greater in the areas adjacent to the nasal processes. Differential rates of decline, rather than acceleration of cell proliferation, therefore, appears to be operative as a morphogenetic mechanism during early primary palate formation.

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LncRNA-uc.167 influences cell proliferation, apoptosis and differentiation of P19 cells by regulating Mef2c

Gene ◽

10.1016/j.gene.2016.06.006 ◽

2016 ◽

Vol 590 (1) ◽

pp. 97-108 ◽

Cited By ~ 22

Author(s):

Guixian Song ◽

Yahui Shen ◽

Zhongbao Ruan ◽

Xing Li ◽

Yumei Chen ◽

...

Keyword(s):

Cell Proliferation ◽

P19 Cells

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LIM kinase inhibitors disrupt mitotic microtubule organization and impair tumor cell proliferation

Oncotarget ◽

10.18632/oncotarget.6288 ◽

2015 ◽

Vol 6 (36) ◽

pp. 38469-38486 ◽

Cited By ~ 18

Author(s):

Katerina Mardilovich ◽

Mark Baugh ◽

Diane Crighton ◽

Dominika Kowalczyk ◽

Mads Gabrielsen ◽

...

Keyword(s):

Cell Proliferation ◽

Tumor Cell ◽

Kinase Inhibitors ◽

Tumor Cell Proliferation ◽

Microtubule Organization ◽

Lim Kinase

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Pericentrin, a highly conserved centrosome protein involved in microtubule organization

Cell ◽

10.1016/0092-8674(94)90504-5 ◽

1994 ◽

Vol 76 (4) ◽

pp. 639-650 ◽

Cited By ~ 382

Author(s):

Stephen J. Doxsey ◽

Pascal Stein ◽

Louise Evans ◽

Patricia D. Calarco ◽

Marc Kirschner

Keyword(s):

Microtubule Organization ◽

Centrosome Protein

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A Ubiquitous β-tubulin Disrupts Microtubule Assembly and Inhibits Cell Proliferation

Molecular Biology of the Cell ◽

10.1091/mbc.e04-01-0060 ◽

2004 ◽

Vol 15 (7) ◽

pp. 3123-3131 ◽

Cited By ~ 60

Author(s):

Rajat Bhattacharya ◽

Fernando Cabral

Keyword(s):

Cell Proliferation ◽

Mammalian Cells ◽

Microtubule Assembly ◽

Microtubule Organization ◽

Class V ◽

Tubulin Isotypes ◽

Concomitant Reduction ◽

Mitotic Spindle Assembly ◽

Dose Dependent ◽

Β Tubulin

Vertebrate tubulin is encoded by a multigene family that produces distinct gene products, or isotypes, of both the α- and β-tubulin subunits. The isotype sequences are conserved across species supporting the hypothesis that different isotypes subserve different functions. To date, however, most studies have demonstrated that tubulin isotypes are freely interchangeable and coassemble into all classes of microtubules. We now report that, in contrast to other isotypes, overexpression of a mouse class V β-tubulin cDNA in mammalian cells produces a strong, dose-dependent disruption of microtubule organization, increased microtubule fragmentation, and a concomitant reduction in cellular microtubule polymer levels. These changes also disrupt mitotic spindle assembly and block cell proliferation. Consistent with diminished microtubule assembly, there is an increased tolerance for the microtubule stabilizing drug, paclitaxel, which is able to reverse many of the effects of class V β-tubulin overexpression. Moreover, transfected cells selected in paclitaxel exhibit increased expression of class V β-tubulin, indicating that this isotype is responsible for the drug resistance. The results show that class V β-tubulin is functionally distinct from other tubulin isotypes and imparts unique properties on the microtubules into which it incorporates.

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