scholarly journals Cell polarity, cell adhesion, and spermatogenesis: role of cytoskeletons

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1565 ◽  
Author(s):  
Linxi Li ◽  
Ying Gao ◽  
Haiqi Chen ◽  
Tito Jesus ◽  
Elizabeth Tang ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Polarity ◽  
Sertoli Cell ◽  
Connexin 43 ◽  
Planar Cell Polarity ◽  
Protein Complexes ◽  
Seminiferous Epithelium ◽  
Cell Junctions ◽  
Adhesion Protein ◽  
Adult Rat

In the rat testis, studies have shown that cell polarity, in particular spermatid polarity, to support spermatogenesis is conferred by the coordinated efforts of the Par-, Crumbs-, and Scribble-based polarity complexes in the seminiferous epithelium. Furthermore, planar cell polarity (PCP) is conferred by PCP proteins such as Van Gogh-like 2 (Vangl2) in the testis. On the other hand, cell junctions at the Sertoli cell–spermatid (steps 8–19) interface are exclusively supported by adhesion protein complexes (for example, α6β1-integrin-laminin-α3,β3,γ3 and nectin-3-afadin) at the actin-rich apical ectoplasmic specialization (ES) since the apical ES is the only anchoring device in step 8–19 spermatids. For cell junctions at the Sertoli cell–cell interface, they are supported by adhesion complexes at the actin-based basal ES (for example, N-cadherin-β-catenin and nectin-2-afadin), tight junction (occludin-ZO-1 and claudin 11-ZO-1), and gap junction (connexin 43-plakophilin-2) and also intermediate filament-based desmosome (for example, desmoglein-2-desmocollin-2). In short, the testis-specific actin-rich anchoring device known as ES is crucial to support spermatid and Sertoli cell adhesion. Accumulating evidence has shown that the Par-, Crumbs-, and Scribble-based polarity complexes and the PCP Vangl2 are working in concert with actin- or microtubule-based cytoskeletons (or both) and these polarity (or PCP) protein complexes exert their effects through changes in the organization of the cytoskeletal elements across the seminiferous epithelium of adult rat testes. As such, there is an intimate relationship between cell polarity, cell adhesion, and cytoskeletal function in the testis. Herein, we critically evaluate these recent findings based on studies on different animal models. We also suggest some crucial future studies to be performed.

scholarly journals 14-3-3 Protein Regulates Cell Adhesion in the Seminiferous Epithelium of Rat Testes

Endocrinology ◽  
2009 ◽  
Vol 150 (10) ◽  
pp. 4713-4723 ◽  
Author(s):  
Elissa W. P. Wong ◽  
Shengyi Sun ◽  
Michelle W. M. Li ◽  
Will M. Lee ◽  
C. Yan Cheng
Keyword(s):  
Cell Adhesion ◽  
Cell Polarity ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Mammalian Cells ◽  
Critical Role ◽  
Seminiferous Epithelium ◽  
General Mechanism ◽  
Permeability Barrier ◽  
Polarity Proteins

Abstract Polarity proteins have been implicated in regulating and maintaining tight junction (TJ) and cell polarity in epithelia. Here we report 14-3-3θ, the homolog of Caenorhabditis elegans Par5 in mammalian cells, which is known to confer cell polarity at TJ, is found at the apical ectoplasmic specialization (ES), a testis-specific adherens junction type restricted to the Sertoli cell-elongating spermatid interface, in which TJ is absent. 14-3-3θ was shown to play a critical role in conferring cell adhesion at the apical ES. A loss of 14-3-3θ expression at the apical ES was detected in the seminiferous epithelium before spermiation. Involvement of 14-3-3θ in Sertoli cell adhesion was confirmed by its knockdown by RNA interference in Sertoli cells cultured in vitro with established TJ permeability barrier that mimicked the blood-testis barrier (BTB) in vivo. Mislocalization of N-cadherin and zonula occludens-1, but not α- and β-catenins, was observed after 14-3-3θ knockdown in Sertoli cells, moving from the cell-cell interface to cytosol, indicating a disruption of cell adhesion. Studies by endocytosis assay illustrated that this loss of cell adhesion was mediated by an increase in the kinetics of endocytosis of N-cadherin and junctional adhesion molecule-A at the BTB, which may represent a general mechanism by which polarity proteins regulate cell adhesion. In summary, the testis is using 14-3-3θ to regulate cell adhesion at the apical ES to facilitate spermiation and at the BTB to facilitate the transit of preleptotene spermatocytes at stages VIII–IX of the epithelial cycle. 14-3-3θ may act as a molecular switch that coordinates these two cellular events in the seminiferous epithelium during spermatogenesis.

scholarly journals New mouse models for high resolution and live imaging of planar cell polarity proteins in vivo

Development ◽  
2021 ◽  
Author(s):  
Lena P. Basta ◽  
Michael Hill-Oliva ◽  
Sarah V. Paramore ◽  
Rishabh Sharan ◽  
Audrey Goh ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Mouse Models ◽  
Planar Cell Polarity ◽  
Protein Complexes ◽  
Protein Localization ◽  
Super Resolution ◽  
Live Imaging ◽  
Cell Junctions ◽  
And Function

The collective polarization of cellular structures and behaviors across a tissue plane is a near universal feature of epithelia known as planar cell polarity (PCP). This property is controlled by the core PCP pathway, which is comprised of highly conserved membrane-associated protein complexes that localize asymmetrically at cell junctions. Here we introduce three new mouse models for investigating the localization and dynamics of transmembrane PCP proteins Celsr1, Fz6, and Vangl2. Using the skin epidermis as a model, we characterize and verify the expression, localization and function of endogenously-tagged Celsr1-3xGFP, Fz6-3xGFP and tdTomato-Vangl2 fusion proteins. Live imaging of Fz6-3xGFP in basal epidermal progenitors reveals that the polarity of the tissue is not fixed through time. Rather asymmetry dynamically shifts during cell rearrangements and divisions, while global, average polarity of the tissue is preserved. We show using super-resolution STED imaging that Fz6-3xGFP and tdTomato-Vangl2 can be resolved, enabling us to observe their complex localization along junctions. We further explore PCP fusion protein localization in the trachea and neural tube, and discover new patterns of PCP expression and localization throughout the mouse embryo.

scholarly journals Ancestral roles of atypical cadherins in planar cell polarity

2020 ◽  
Vol 117 (32) ◽  
pp. 19310-19320
Author(s):  
Maria Brooun ◽  
Alexander Klimovich ◽  
Mikhail Bashkurov ◽  
Bret J. Pearson ◽  
Robert E. Steele ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Sister Group ◽  
The Body ◽  
Cell Alignment ◽  
Actin Organization ◽  
Tissue Organization ◽  
Ancestral Function ◽  
Local Cell

Fat, Fat-like, and Dachsous family cadherins are giant proteins that regulate planar cell polarity (PCP) and cell adhesion in bilaterians. Their evolutionary origin can be traced back to prebilaterian species, but their ancestral function(s) are unknown. We identified Fat-like and Dachsous cadherins inHydra, a member of phylum Cnidaria a sister group of bilaterian. We foundHydradoes not possess a true Fat homolog, but has homologs of Fat-like (HyFatl) and Dachsous (HyDs) that localize at the apical membrane of ectodermal epithelial cells and are planar polarized perpendicular to the oral–aboral axis of the animal. Using a knockdown approach we found that HyFatl is involved in local cell alignment and cell–cell adhesion, and that reduction of HyFatl leads to defects in tissue organization in the body column. Overexpression and knockdown experiments indicate that the intracellular domain (ICD) of HyFatl affects actin organization through proline-rich repeats. Thus, planar polarization of Fat-like and Dachsous cadherins has ancient, prebilaterian origins, and Fat-like cadherins have ancient roles in cell adhesion, spindle orientation, and tissue organization.

scholarly journals Coordination of Actin- and Microtubule-Based Cytoskeletons Supports Transport of Spermatids and Residual Bodies/Phagosomes During Spermatogenesis in the Rat Testis

Endocrinology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 47-62 ◽  
Author(s):  
Elizabeth I. Tang ◽  
Will M. Lee ◽  
C. Yan Cheng
Keyword(s):  
Germ Cell ◽  
Regulatory Protein ◽  
Growth Factor Receptor ◽  
Seminiferous Epithelium ◽  
Cell Junctions ◽  
Related Protein ◽  
Cell Transport ◽  
Adult Rat ◽  
Residual Bodies ◽  
Actin Regulatory Proteins

Abstract Germ cell transport across the seminiferous epithelium during spermatogenesis requires the intricate coordination of cell junctions, signaling proteins, and both actin- and microtubule (MT)-based cytoskeletons. Although the involvement of cytoskeletons in germ cell transport has been suggested, the precise mechanism(s) remains elusive. Based on growing evidencethat actin and MT interactions underlie fundamental cellular processes, such as cell motility, it is unlikely that actin- and MT-based cytoskeletons work independently to regulate germ cell transport in the testis. Using rats treated with adjudin, a potential male contraceptive that disrupts spermatid adhesion and transport in the testis, as a study model, we show herein that actin- and MT-based cytoskeletons are both necessary for transport of spermatids and residual bodies/phagosomes across the seminiferous epithelium in adult rat testes. Analysis of intratubular expression of F-actin and tubulin revealed disruption of both actin and MT networks, concomitant with misdirected spermatids and phagosomes in rats treated with adjudin. Actin regulatory proteins, epidermal growth factor receptor pathway substrate 8 and actin-related protein 3, were mislocalized and down-regulated at the actin-rich anchoring junction between germ and Sertoli cells (apical ectoplasmicspecialization) after adjudin treatment. Nonreceptor tyrosine kinase p-FAK-Tyr407, known to regulate F-actin nucleation via actin-related protein 3, was also mislocalized and down-regulated at the apical ectoplasmic specialization, corroborating the observation of actin cytoskeleton disruption. Additionally, spatiotemporal expression of MT regulatory protein end-binding protein 1, shown to be involved in MT-actin cross talk herein, was also disrupted after adjudin treatment. In summary, spermatid/phagosome transport across the epithelium during spermatogenesis requires the coordination between actin- and MT-based cytoskeletons. (Endocrinology 157: 1644–1659, 2016)

scholarly journals Neural Cell Adhesion Molecule (N-CAM) Is Required for Cell Type Segregation and Normal Ultrastructure in Pancreatic Islets

1999 ◽  
Vol 144 (2) ◽  
pp. 325-337 ◽  
Author(s):  
Farzad Esni ◽  
Inge-Bert Täljedal ◽  
Anne-Karina Perl ◽  
Harold Cremer ◽  
Gerhard Christofori ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Pancreatic Islets ◽  
Cell Polarity ◽  
Adhesion Molecule ◽  
Islet Cell ◽  
Cell Adhesion Molecule ◽  
Cell Junctions ◽  
Cell Type ◽  
Deficient Mice ◽  
Cell Cell

Classical cell dissociation/reaggregation experiments with embryonic tissue and cultured cells have established that cellular cohesiveness, mediated by cell adhesion molecules, is important in determining the organization of cells within tissue and organs. We have employed N-CAM-deficient mice to determine whether N-CAM plays a functional role in the proper segregation of cells during the development of islets of Langerhans. In N-CAM-deficient mice the normal localization of glucagon-producing α cells in the periphery of pancreatic islets is lost, resulting in a more randomized cell distribution. In contrast to the expected reduction of cell–cell adhesion in N-CAM-deficient mice, a significant increase in the clustering of cadherins, F-actin, and cell–cell junctions is observed suggesting enhanced cadherin-mediated adhesion in the absence of proper N-CAM function. These data together with the polarized distribution of islet cell nuclei and Na+/K+-ATPase indicate that islet cell polarity is also affected. Finally, degranulation of β cells suggests that N-CAM is required for normal turnover of insulin-containing secretory granules. Taken together, our results confirm in vivo the hypothesis that a cell adhesion molecule, in this case N-CAM, is required for cell type segregation during organogenesis. Possible mechanisms underlying this phenomenon may include changes in cadherin-mediated adhesion and cell polarity.

BLOOD–TESTIS BARRIER: EVIDENCE FOR INTACT INTER-SERTOLI CELL JUNCTIONS AFTER HYPOPHYSECTOMY IN THE ADULT RAT

1978 ◽  
Vol 76 (1) ◽  
pp. 87-91 ◽  
Author(s):  
L. HAGENÄS ◽  
L. PLÖEN ◽  
H. EKWALL
Keyword(s):  
Sertoli Cell ◽  
Structural Integrity ◽  
Cell Junctions ◽  
Junctional Complex ◽  
Tracer Technique ◽  
Adult Rats ◽  
Adult Rat ◽  
Hormonal Dependence ◽  
Lanthanum Tracer ◽  
Blood Testis Barrier

SUMMARY To study the hormonal dependence of the blood–testis barrier, adult rats were hypophysectomized and the ultrastructural integrity of the inter-Sertoli cell junctional complex was examined at various times with a lanthanum tracer technique. It was found that the structural integrity of the inter-Sertoli cell junctions and their capacity to exclude lanthanum from the adluminal compartment were preserved up to 35 days after hypophysectomy. Furthermore, transport of newly formed spermatocytes through the inter-Sertoli cell junctions still occurred 20 days after hypophysectomy. It is therefore concluded that the function of the inter-Sertoli cell junctional complex is not directly dependent on gonadotrophic or androgenic hormones, but is regulated by other mechanisms.

scholarly journals c-Yes regulates cell adhesion at the apical ectoplasmic specialization-blood-testis barrier axis via its effects on protein recruitment and distribution

2013 ◽  
Vol 304 (2) ◽  
pp. E145-E159 ◽  
Author(s):  
Xiang Xiao ◽  
Dolores D. Mruk ◽  
C. Yan Cheng
Keyword(s):  
Cell Adhesion ◽  
Sertoli Cell ◽  
Germ Cells ◽  
Early Stage ◽  
Seminiferous Epithelium ◽  
Permeability Barrier ◽  
Cell Interface ◽  
Ectoplasmic Specialization ◽  
Cell Cell ◽  
Blood Testis Barrier

During spermatogenesis, extensive restructuring takes place at the cell-cell interface since developing germ cells migrate progressively from the basal to the adluminal compartment of the seminiferous epithelium. Since germ cells per se are not motile cells, their movement relies almost exclusively on the Sertoli cell. Nonetheless, extensive exchanges in signaling take place between these cells in the seminiferous epithelium. c-Yes, a nonreceptor protein tyrosine kinase belonging to the Src family kinases (SFKs) and a crucial signaling protein, was recently shown to be upregulated at the Sertoli cell-cell interface at the blood-testis barrier (BTB) at stages VIII–IX of the seminiferous epithelial cycle of spermatogenesis. It was also highly expressed at the Sertoli cell-spermatid interface known as apical ectoplasmic specialization (apical ES) at stage V to early stage VIII of the epithelial cycle during spermiogenesis. Herein, it was shown that the knockdown of c-Yes by RNAi in vitro and in vivo affected both Sertoli cell adhesion at the BTB and spermatid adhesion at the apical ES, causing a disruption of the Sertoli cell tight junction-permeability barrier function, germ cell loss from the seminiferous epithelium, and also a loss of spermatid polarity. These effects were shown to be mediated by changes in distribution and/or localization of adhesion proteins at the BTB (e.g., occludin, N-cadherin) and at the apical ES (e.g., nectin-3) and possibly the result of changes in the underlying actin filaments at the BTB and the apical ES. These findings implicate that c-Yes is a likely target of male contraceptive research.

scholarly journals Ancestral role of Fat-like cadherins in planar cell polarity

2019 ◽  
Author(s):  
Maria Brooun ◽  
Alexander Klimovich ◽  
Mikhail Bashkurov ◽  
Bret J. Pearson ◽  
Robert E. Steele ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Radial Symmetry ◽  
Global Alignment ◽  
Cell Alignment ◽  
Tissue Organization ◽  
Ancestral Function ◽  
Simple Body ◽  
Epithelial Layers

ABSTRACTFat family cadherins are enormous proteins that regulate planar cell polarity (PCP) and cell adhesion in bilaterian animals. Their evolutionary origin can be traced back to prebilaterian species, but their ancestral function(s) are unknown. We identified Fat-like and Dachsous cadherins in Hydra, a member of the early-diverging metazoan phylum Cnidaria. Hydra has a simple body plan with only two epithelial layers and radial symmetry. We find that Hydra homologues of Fat-like (HyFat) and Dachsous (HyDs) co-localize at the apico-lateral membrane of ectodermal epithelial cells. Remarkably, HyFat is planar polarized perpendicular to the oral-aboral axis of the animal. Using knockdown approaches we found that HyFat is involved in the regulation of local cell alignment, but is dispensable for the global alignment of ectodermal myonemes along the oral-aboral axis. The intracellular domain (ICD) of HyFat is involved in the morphogenesis of ectodermal myonemes. Thus, Fat family cadherins have ancient, prebilaterian functions in cell adhesion, tissue organization and planar polarity.

Sign in / Sign up

Export Citation Format

Share Document