Keratin polypeptides in the epidermis of the larval (ammocoete) sea lamprey, Petromyzon marinus L., show a cell type-specific immunolocalization

1994 ◽  
Vol 72 (1) ◽  
pp. 190-194 ◽  
Author(s):  
V. B. Alarcón ◽  
M. F. Filosa ◽  
J. H. Youson

Using immunofluorescent staining, the localization of keratin polypeptides in the epidermis of the larval (ammocoete) sea lamprey, Petromyzon marinus L., is described. Immunostaining with monoclonal antibodies against human keratin polypeptides showed that immunoreactivity was distributed in a cell type-specific pattern among the epidermal cells of ammocoete skin: immunoreactivity for keratin polypeptides Nos. 7 and 18 was prominent in skein and granular cells, respectively, while that for keratin polypeptide No. 19 was in cytoplasmic regions near the plasma membrane of both specialized (skein, granular, and mucous) and germinal cells. Positive immunostaining with a polyclonal antibody against bovine keratins suggests that there are other, as yet unidentified, keratin polypeptides in the epidermis. The significance of keratins as molecular markers of epidermal development is discussed.

2021 ◽  
Author(s):  
Jaesoo Jung ◽  
Jhon R Enterina ◽  
Duong T Bui ◽  
Fahima Mozaneh ◽  
Po-Han Lin ◽  
...  

The immunomodulatory family of Siglecs recognize sialic acid-containing glycans as self, which is exploited in cancer for immune-evasion. The biochemical nature of Siglec ligands remains incompletely understood with emerging evidence suggesting the importance of carbohydrate sulfation. Here, we investigate how specific sulfate modifications affect Siglec ligands by overexpressing eight carbohydrate sulfotransferases (CHSTs) in five cell lines. Overexpression of three CHSTs (CHST1, CHST2, or CHST4) significantly enhances the binding of numerous Siglecs. Unexpectedly, two other CHSTs (Gal3ST2 and Gal3ST3) diminish Siglec binding, suggesting a new mode to modulate Siglec ligands via sulfation. Results are cell type dependent, indicating that the context in which sulfated glycans are presented is important. Moreover, pharmacological blockade of N- and O-glycan maturation reveals a cell type-specific pattern of importance for either class of glycan. Production of a highly homogenous CD33 (Siglec-3) fragment enabled a mass spectrometry-based binding assay to determine 10-fold and 3-fold enhanced affinity for Neu5Acα2-3(6-O-sulfo)Galβ1-4GlcNAc and Neu5Acα2-3Galβ1-4(6-O-sulfo)GlcNAc, respectively, over Neu5Acα2-3Galβ1-4GlcNAc. CD33 showed significant additivity in affinity (36-fold) for the disulfated ligand, Neu5Acα2-3(6-O-sulfo)Galβ1-4(6-O-sulfo)GlcNAc. Moreover, overexpression of both CHST1 and CHST2 in cells greatly enhanced the binding of several Siglecs, including CD33. Finally, we reveal that CHST1 is upregulated in numerous cancers, correlating with poorer survival rates and sodium chlorate sensitivity for the binding of Siglecs to cancer cell lines. These results provide new insights into carbohydrate sulfation as a modification that is a general mechanism for tuning Siglec ligands on cells, including in cancer.


2017 ◽  
Vol 55 (05) ◽  
pp. e28-e56
Author(s):  
S Macheiner ◽  
R Gerner ◽  
A Pfister ◽  
A Moschen ◽  
H Tilg

2020 ◽  
Vol 528 (13) ◽  
pp. 2218-2238 ◽  
Author(s):  
Attilio Iemolo ◽  
Patricia Montilla‐Perez ◽  
I‐Chi Lai ◽  
Yinuo Meng ◽  
Syreeta Nolan ◽  
...  

2021 ◽  
Author(s):  
Moataz Dowaidar

Autophagy is a double-edged sword in cancer, and numerous aspects should be taken into account before deciding on the most effective strategy to target the process. The fact that several clinical studies are now ongoing does not mean that the patient group that may benefit from autophagy-targeting medicines has been identified. Autophagy inhibitors that are more potent and specialized, as well as autophagy indicators, are also desperately required. The fact that these inhibitors only work against tumors that rely on autophagy for survival (RAS mutants) makes it difficult to distinguish them from tumors that continue to develop even when autophagy is absent. Furthermore, mutations such as BRAF have been shown to make tumors more susceptible to autophagy suppression, suggesting that targeting such tumours may be a viable strategy for overcoming their chemotherapy resistance. In the meantime, we are unable to identify if autophagy regulation works in vivo or whether it selectively targets a disease while inflicting injury to other healthy organs and tissues. A cell-type-specific impact appears to be observed with such therapy. As a result, it is just as important to consider the differences between tumors that originate in different organs as it is to consider the signaling pathways that are similar across them. For a therapy or cure to be effective, the proposed intervention must be tailored to the specific needs of each patient.Over the last several years, a growing amount of data has implicated autophagy in a variety of disorders, including cancer. In normal cells, this catabolic process is also required for cell survival and homeostasis. Despite the fact that medications targeting intermediates in the autophagy signaling pathway are being created and evaluated at both the preclinical and clinical levels, given the complicated function of autophagy in cancer, we still have a long way to go in terms of establishing an effective therapeutic approach. This article discusses current tactics for exploiting cancer cells' autophagy dependency, as well as obstacles in the area. We believe that the unanswered concerns raised in this work will stimulate researchers to investigate previously unknown connections between autophagy and other signaling pathways, which might lead to the development of novel, highly specialized autophagy therapies.


1993 ◽  
Vol 13 (9) ◽  
pp. 5301-5314 ◽  
Author(s):  
G S Huh ◽  
R O Hynes

We have investigated the regulation of splicing of one of the alternatively spliced exons in the rat fibronectin gene, the EIIIB exon. This 273-nucleotide exon is excluded by some cells and included to various degrees by others. We find that EIIIB is intrinsically poorly spliced and that both its exon sequences and its splice sites contribute to its poor recognition. Therefore, cells which recognize the EIIIB exon must have mechanisms for improving its splicing. Furthermore, in order for EIIB to be regulated, a balance must exist between the EIIIB splice sites and those of its flanking exons. Although the intron upstream of EIIIB does not appear to play a role in the recognition of EIIIB for splicing, the intron downstream contains sequence elements which can promote EIIIB recognition in a cell-type-specific fashion. These elements are located an unusually long distance from the exon that they regulate, more than 518 nucleotides downstream from EIIIB, and may represent a novel mode of exon regulation.


2000 ◽  
Vol 191 (8) ◽  
pp. 1281-1292 ◽  
Author(s):  
Raelene J. Grumont ◽  
Steve Gerondakis

In lymphocytes, the Rel transcription factor is essential in establishing a pattern of gene expression that promotes cell proliferation, survival, and differentiation. Here we show that mitogen-induced expression of interferon (IFN) regulatory factor 4 (IRF-4), a lymphoid-specific member of the IFN family of transcription factors, is Rel dependent. Consistent with IRF-4 functioning as a repressor of IFN-induced gene expression, the absence of IRF-4 expression in c-rel−/− B cells coincided with a greater sensitivity of these cells to the antiproliferative activity of IFNs. In turn, enforced expression of an IRF-4 transgene restored IFN modulated c-rel−/− B cell proliferation to that of wild-type cells. This cross-regulation between two different signaling pathways represents a novel mechanism that Rel/nuclear factor κB can repress the transcription of IFN-regulated genes in a cell type–specific manner.


1974 ◽  
Vol 52 (12) ◽  
pp. 1585-1589 ◽  
Author(s):  
J. C. George ◽  
F. W. H. Beamish

The supraneural myeloid body of the sea lamprey (Petromyzon marinus) was studied in the feeding adult, late spawning run adult, and metamorphosing ammocoete. The fatty nature of the tissue was established by histochemical staining and electron microscopy. The presence of the fat cells and the actively differentiating blood cells evinced its similarity to the bone marrow in higher animals, thereby suggesting a phylogenetic affinity. In the late spawning run lampreys, the tissue was found to be almost empty of blood cells, leaving empty spaces within the stromal skeleton. In the feeding adult tissue, the various blood cell types differentiated from precursor cells have been identified. Megakaryoblasts possibly representing early phases of the cell type were observed only in the transforming (macrophthalmia stage) and adult lampreys. A marked active development of the tissue in the ammocoete was seen only at the fourth stage of the metamorphosing ammocoete immediately before macrophthalmia. At the macrophthalmia stage, the haematopoietic activity in the tissue increased substantially.


2018 ◽  
Vol 25 (3) ◽  
pp. 1143-1152 ◽  
Author(s):  
Yunmei Zhang ◽  
Jieru Xu ◽  
Dairong Li ◽  
Tao Wan ◽  
Qianfang Hu

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