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Apc and primary cilia

P Chandorkar, W Posch, V Zaderer, M Blatzer, M Steger, C G Ammann, U Binder, M Hermann, P Hörtnagl, C Lass-Flörl, D Wilflingseder
To study interactions of airborne pathogens, e.g. Aspergillus (A.) fumigatus with upper and lower respiratory tract epithelial and immune cells, we set up a perfused 3D human bronchial and small airway epithelial cell system. Culturing of normal human bronchial or small airway epithelial (NHBE, SAE) cells under air liquid interphase (ALI) and perfusion resulted in a significantly accelerated development of the lung epithelia associated with higher ciliogenesis, cilia movement, mucus-production and improved barrier function compared to growth under static conditions...
September 14, 2017: Scientific Reports
Akshari Gupta, Yuki Tsuchiya, Midori Ohta, Gen Shiratsuchi, Daiju Kitagawa
The decision to commit to the cell cycle is made during G1 through the concerted action of various cyclin-CDK complexes. Not only DNA replication, but also centriole duplication is initiated as cells enter the S-phase. The NIMA-related kinase NEK7 is one of many factors required for proper centriole duplication, as well as for timely cell cycle progression. However, its specific roles in these events are poorly understood. In this study, we find that depletion of NEK7 inhibits progression through the G1 phase in human U2OS cells via down-regulation of various cyclins and CDKs and also inhibits the earliest stages of procentriole formation...
July 15, 2017: Molecular Biology of the Cell
Eugenio Bustos-Morán, Noelia Blas-Rus, Noa Beatriz Martin-Cófreces, Francisco Sánchez-Madrid
The immune synapse (IS) is a specialized structure formed at the contact area between T lymphocytes and antigen-presenting cells (APCs) that is essential for the adaptive immune response. Proper T cell activation requires its polarization towards the APC, which is highly dependent on the tubulin cytoskeleton. Microtubule-associated protein-4 (MAP4) is a microtubule (MT)-stabilizing protein that controls MTs in physiological processes, such as cell division, migration, vesicular transport or primary cilia formation...
April 1, 2017: Journal of Cell Science
Li Song, Yuxin Jia, Wensi Zhu, Ian P Newton, Zhuoyu Li, Wenling Li
Adenomatous polyposis coli (APC) gene is a tumor suppressor gene and its truncated mutations cause a few cilia-related diseases such as Gardner's syndrome. However, little is known about the mechanism that links APC mutations and cilia disorder. APC mutations lead to the expression of N-terminal fragments, which have dominant effects in tumors owing to loss of the C-terminal region or a gain of function. The present study investigated the impact of tumor-associated N-terminal APC fragments on primary cilia assembly and the possible molecular mechanism involved...
October 2014: International Journal of Biochemistry & Cell Biology
Weiping Wang, Tao Wu, Marc W Kirschner
The primary cilium has an important role in signaling; defects in structure are associated with a variety of human diseases. Much of the most basic biology of this organelle is poorly understood, even basic mechanisms, such as control of growth and resorption. We show that the activity of the anaphase-promoting complex (APC), an E3 that regulates the onset of anaphase, destabilizes axonemal microtubules in the primary cilium. Furthermore, the metaphase APC co-activator, Cdc20, is specifically recruited to the basal body of primary cilia...
August 19, 2014: ELife
Soeren Lienkamp, Athina Ganner, Gerd Walz
Mutations of the ankyrin-repeat protein Inversin, a member of a diverse family of more than 12 proteins, cause nephronophthisis (NPH), an autosomal recessive cystic kidney disease associated with extra-renal manifestations such as retinitis pigmentosa, cerebellar aplasia and situs inversus. Most NPH gene products (NPHPs) localize to the cilium, and appear to control the transport of cargo protein to the cilium by forming functional networks. Inversin interacts with NPHP1 and NPHP3, and shares with NPHP4 the ability to antagonize Dishevelled-stimulated canonical Wnt signaling, potentially through recruitment of the Anaphase Promoting Complex (APC/C)...
February 2012: Differentiation; Research in Biological Diversity
Peter Satir
Quyn and colleagues report that gut stem cells have a biased spindle orientation and asymmetric retention of label-retaining DNA. These features are lost in mouse and human tissues when the microtubule binding protein Apc is mutated. In the developing kidney, Apc acts downstream from primary cilium signaling to influence spindle orientation when noncanonical Wnt signaling predominates. Do gut stem cells also have primary cilia?
2010: Stem Cell Research & Therapy
J Iglesias Alzueta, N Matamoros Florí
Common variable immunodeficiency (CVI) is a primary immunodeficiency characterized by deficient antibody production. The cause of this immunodeficiency is unknown; several in vitro studies have revealed a significant number of alterations that could explain the hypogammaglobulinemia present in this syndrome. Among those described are primary B cell alterations, numerical and functional T cell abnormalities, and defects in the interaction between accessory cells. The alteration typical of CVI is the failure of B lymphocytes to differentiate from antibody-producing cells, resulting in deficient immunoglobulin secretion...
May 2001: Allergologia et Immunopathologia
G A Rossi, O Sacco, B Balbi, S Oddera, T Mattioni, G Corte, C Ravazzoni, L Allegra
HLA-DR class II molecules are expressed by a variety of nonlymphoid cells, including the respiratory epithelium. However, it is not known if ciliated bronchial epithelial cells express the HLA-DR genes, if the expression of class II molecules on their surface can be modulated by immune mediators and, finally, if these cells, like other HLA-DR-positive epithelial cells, have the potential to serve as antigen-presenting cells. To answer these questions, we collected ciliated bronchial epithelial cells by brushing and by suction during fiberoptic bronchoscopy and by scraping surgically resected bronchi...
November 1990: American Journal of Respiratory Cell and Molecular Biology
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