scholarly journals KIF5B modulates central spindle organization in late-stage cytokinesis in chondrocytes

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Huiyan Gan ◽  
Wenqian Xue ◽  
Ya Gao ◽  
Guixia Zhu ◽  
Danny Chan ◽  
...  
Keyword(s):  
Family Member ◽  
Growth Plate ◽  
Intracellular Transport ◽  
Primary Cilia ◽  
Microtubule Network ◽  
Central Spindle ◽  
Columnar Organization ◽  
Cell Rotation ◽  
Cilia Formation ◽  
Kinesin Family

Abstract Background The growth plate is a special region of the cartilage that drives longitudinal growth of long bones. Proliferating chondrocytes in the growth plate, arranged in columns, divide perpendicular to the long axis of the growth plate then intercalate to re-align with parental columns. Which molecular partners maintain growth plate columnar structures and chondrocyte cytokinesis has not been fully revealed. It is reported that kinesin family member 3A (KIF3A), a subunit of kinesin-2, plays an important role in maintaining columnar organization in growth plates via controlling primary cilia formation and cell proliferation. Result Here we identify kinesin family member 5B (KIF5B), the heavy chain of kinesin-1, a ubiquitously expressed motor protein for anterograde intracellular transport along the microtubule network, as a key modulator of cytokinesis in chondrocytes via maintenance of central spindle organization. We show that KIF5B is concentrated in the central spindle during cytokinesis in both primary chondrocytes and chondrogenic ATDC5 cells. Conclusion The failure of cytokinesis in KIF5B null chondrocytes leads to incomplete cell rotation, disrupting proliferation and differentiation, and results in a disorganized growth plate.

scholarly journals Trisomy 21 increases microtubules and disrupts centriolar satellite localization

2021 ◽  
Author(s):  
Bailey L McCurdy ◽  
Cayla E Jewett ◽  
Alexander J StemmWolf ◽  
Huy Nguyen Duc ◽  
Molishree Joshi ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Intracellular Trafficking ◽  
Trisomy 21 ◽  
Primary Cilia ◽  
Chromosome 21 ◽  
Normal Density ◽  
Wild Type ◽  
Microtubule Network ◽  
Cilia Formation

Trisomy 21, the cause of Down syndrome, causes a 0.5-fold protein increase of the chromosome 21-resident gene Pericentrin (PCNT) and reduces primary cilia formation and signaling. Here we investigate the mechanisms by which PCNT imbalances disrupt cilia. Using isogenic RPE-1 cells with increased chromosome 21 dosage, we find PCNT protein accumulates around the centrosome as a pericentrosomal cluster of enlarged cytoplasmic puncta that localize along and at MT ends. Cytoplasmic PCNT puncta impact the intracellular MT trafficking network required for primary cilia, as the PCNT puncta sequester cargo peripheral to centrosomes in what we call pericentrosomal crowding. The centriolar satellite proteins, PCM1, CEP131 and CEP290, important for ciliogenesis, accumulate at sites of enlarged PCNT puncta in trisomy 21 cells. Reducing PCNT when chromosome 21 ploidy is elevated is sufficient to decrease PCNT puncta, reestablish a normal density of MTs around the centrosome, restore ciliogenesis to wild type levels and decrease pericentrosomal crowding. A transient reduction in MTs also decreases pericentrosomal crowding and partially rescues ciliogenesis in trisomy 21 cells, indicating that increased PCNT leads to defects in the microtubule network deleterious to normal centriolar satellite distribution. We propose that chromosome 21 aneuploidy disrupts MT-dependent intracellular trafficking required for primary cilia.

scholarly journals Protein Kinase A-Mediated Septin7 Phosphorylation Disrupts Septin Filaments and Ciliogenesis

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 361
Author(s):  
Han-Yu Wang ◽  
Chun-Hsiang Lin ◽  
Yi-Ru Shen ◽  
Ting-Yu Chen ◽  
Chia-Yih Wang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Primary Cilia ◽  
Cell Growth And Migration ◽  
Filament Dynamics ◽  
Gtp Binding ◽  
Cilia Formation ◽  
And Migration ◽  
Septin Filament ◽  
Kinase A

Septins are GTP-binding proteins that form heteromeric filaments for proper cell growth and migration. Among the septins, septin7 (SEPT7) is an important component of all septin filaments. Here we show that protein kinase A (PKA) phosphorylates SEPT7 at Thr197, thus disrupting septin filament dynamics and ciliogenesis. The Thr197 residue of SEPT7, a PKA phosphorylating site, was conserved among different species. Treatment with cAMP or overexpression of PKA catalytic subunit (PKACA2) induced SEPT7 phosphorylation, followed by disruption of septin filament formation. Constitutive phosphorylation of SEPT7 at Thr197 reduced SEPT7‒SEPT7 interaction, but did not affect SEPT7‒SEPT6‒SEPT2 or SEPT4 interaction. Moreover, we noted that SEPT7 interacted with PKACA2 via its GTP-binding domain. Furthermore, PKA-mediated SEPT7 phosphorylation disrupted primary cilia formation. Thus, our data uncover the novel biological function of SEPT7 phosphorylation in septin filament polymerization and primary cilia formation.

scholarly journals Intracellular Transport Dynamics of Endosomes Containing DNA Polyplexes along the Microtubule Network

2006 ◽  
Vol 90 (5) ◽  
pp. L42-L44 ◽  
Author(s):  
Rajan P. Kulkarni ◽  
Kenneth Castelino ◽  
Arun Majumdar ◽  
Scott E. Fraser
Keyword(s):  
Intracellular Transport ◽  
Microtubule Network ◽  
Transport Dynamics

scholarly journals Mutations in Kinesin family member 6 reveal specific role in ependymal cell ciliogenesis and human neurological development

PLoS Genetics ◽  
2018 ◽  
Vol 14 (11) ◽  
pp. e1007817 ◽  
Author(s):  
Mia J. Konjikusic ◽  
Patra Yeetong ◽  
Curtis W. Boswell ◽  
Chanjae Lee ◽  
Elle C. Roberson ◽  
...  
Keyword(s):  
Family Member ◽  
Ependymal Cell ◽  
Specific Role ◽  
Neurological Development ◽  
Kinesin Family

scholarly journals FBW7 couples structural integrity with functional output of primary cilia

2020 ◽  
Author(s):  
Eleni Petsouki ◽  
Vasileios Gerakopoulos ◽  
Nicholas Szeto ◽  
Wenhan Chang ◽  
Mary Beth Humphrey ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Structural Integrity ◽  
Stem Cell Differentiation ◽  
Bone Architecture ◽  
Structural Defects ◽  
Independent Manner ◽  
Mesenchymal Stem Cell Differentiation ◽  
Cilia Formation ◽  
Length Changes ◽  
Msc Differentiation

AbstractStructural defects in cilia have robust effects in diverse tissues and systems. However, how ciliary length changes influence signaling output are unknown. Here, we examined the functional role of a ciliary length control mechanism whereby FBW7-mediated destruction of NDE1 positively regulated ciliary length, in mesenchymal stem cell differentiation. We show that FBW7 functions as a master regulator of both negative (NDE1) and positive (TALPID3) regulators of ciliogenesis, with an overall positive net effect on cilia formation, MSC differentiation, and bone architecture. Deletion of Fbxw7 suppresses ciliation, Hedgehog activity, and differentiation, which are rescued in Fbxw7/Nde1-null cells. However, despite formation of abnormally long cilia in Nde1-null cells, MSC differentiation is suppressed. NDE1 promotes MSC differentiation by increasing the activity of the Hedgehog pathway by direct binding and enhancing GLI2 activity in a cilia-independent manner. We propose that ciliary structure-function coupling is determined by intricate interactions of structural and functional proteins.

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