Cells from Peripheral Tissues that Exhibit High APP Expression are Characterized by their High Membrane Fusion Activity

Beer, J.; Masters, Colin L.; Beyreuther, Konrad

doi:10.1006/neur.1995.0006

Cited by 23 publications

(14 citation statements)

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“…The detection of APP has been reported in the exocrine and endocrine pancreas by immunohistochemistry and in-situ hybridization, respectively (Beer, et al 1995; Figueroa, et al 2001). Additionally, a rigorous analysis of mice lacking APP (APP −/− ) and/or the related APLP2 gene shows changes in circulating blood glucose concentrations (Needham, et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Amyloid precursor protein in pancreatic islets

Kulas

Puig

Combs

2017

Journal of Endocrinology

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The amyloid precursor protein (APP) has been extensively investigated for its role in the production of amyloid beta (Aβ), a plaque forming peptide in Alzheimer’s disease (AD). Epidemiological evidence suggests type 2 diabetes is a risk factor for AD. The pancreas is an essential regulator of blood glucose levels through the secretion of the hormones insulin and glucagon. Pancreatic dysfunction is a well characterized consequence of type 1 and type 2 diabetes. In this study we have examined the expression and processing of pancreatic APP to test the hypothesis that APP may play a role in pancreatic function and the pathophysiology of diabetes. Our data demonstrates the presence of APP within the pancreas, including pancreatic islets in both mouse and human samples. Additionally, we report that the APP/PS1 mouse model of AD overexpresses APP within pancreatic islets, although this did not result in detectable levels of Aβ. We compared whole pancreas and islet culture lysates by western blot from C57BL/6 (WT), APP−/−, and APP/PS1 mice and observed APP-dependent differences in the total protein levels of GLUT4, IDE and BACE2. Immunohistochemistry for BACE2 detected high levels in pancreatic α cells. Additionally, both mouse and human islets processed APP to release sAPP into cell culture media. Moreover, sAPP stimulated insulin but not glucagon secretion from islet cultures. We conclude that APP and its metabolites are capable of influencing the basic physiology of the pancreas, possibly through the release of sAPP acting in an autocrine or paracrine manner.

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Section: Introductionmentioning

confidence: 99%

Amyloid precursor protein in pancreatic islets

Kulas

Puig

Combs

2017

Journal of Endocrinology

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“…APP is a transmembrane protein, the cleavage of which generates peptides, some of which are associated with Alzheimer's disease. APP is produced by cells with a high membrane fusion activity ( i.e ., membrane turnover activity), including Sertoli cells [69], suggesting a role in the maintenance of cellular integrity. In other studies, APP has been detected in the acrosome and the growing tail of spermatids in rat seminiferous tubules [70] and in the head and tail of human spermatozoa [71], suggesting a role in sperm function.…”

Section: Discussionmentioning

confidence: 99%

An Integrative Omics Strategy to Assess the Germ Cell Secretome and to Decipher Sertoli-Germ Cell Crosstalk in the Mammalian Testis

et al. 2014

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Mammalian spermatogenesis, which takes place in complex testicular structures called seminiferous tubules, is a highly specialized process controlled by the integration of juxtacrine, paracrine and endocrine information. Within the seminiferous tubules, the germ cells and Sertoli cells are surrounded by testicular fluid (TF), which probably contains most of the secreted proteins involved in crosstalk between these cells. It has already been established that germ cells can modulate somatic Sertoli cell function through the secretion of diffusible factors. We studied the germ cell secretome, which was previously considered inaccessible, by analyzing the TF collected by microsurgery in an “integrative omics” strategy combining proteomics, transcriptomics, genomics and interactomics data. This approach identified a set of proteins preferentially secreted by Sertoli cells or germ cells. An interaction network analysis revealed complex, interlaced cell-cell dialog between the secretome and membranome of seminiferous cells, mediated via the TF. We then focused on germ cell-secreted candidate proteins, and we identified several potential interacting partners located on the surface of Sertoli cells. Two interactions, APOH/CDC42 and APP/NGFR, were validated in situ, in a proximity ligation assay (PLA). Our results provide new insight into the crosstalk between germ cells and Sertoli cells occurring during spermatogenesis. Our findings also demonstrate that this “integrative omics” strategy is powerful enough for data mining and highlighting meaningful cell-cell communication events between different types of cells in a complex tissue, via a biological fluid. This integrative strategy could be applied more widely, to gain access to secretomes that have proved difficult to study whilst avoiding the limitations of in vitro culture.

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“…Likewise, Beer et al (68) reported the immunohistochemical localization of yet another neurodegenerative protein that is involved in Alzheimer's disease known as amyloid precursor protein in Sertoli cells, follicle cells, and macrophages. Because of the ubiquitous expression of amyloid precursor protein in several different cell types, it was speculated that amyloid precursor protein may be involved in tissue maintenance and repair (68).…”

Section: Discussionmentioning

confidence: 99%

Sertolin Is a Novel Gene Marker of Cell-Cell Interactions in the Rat Testis

Mruk¹,

Cheng²

1999

Journal of Biological Chemistry

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A novel testicular protein designated sertolin was cloned. The full-length sertolin cDNA consists of 853 base pairs with an open reading frame of 381 base pairs coding for a 127-amino acid polypeptide that shares limited identities with antaxin/josephin and thrombospondin proteins. Sertolin (calculated molecular mass, 13,759 daltons) has two mRNA transcripts of 2.3 and 1 kilobase. A 22-amino acid peptide based on the deduced amino acid sequence of sertolin (NH 2 -KKEHFNLFKAASVSHLVQV-VPQ) was synthesized and used for polyclonal antibody production. Immunoblot analysis detected a 17-kDa immunoreactive band in the Sertoli cell cytosol. Using Sertoli-germ cell cocultures, sertolin expression was found to be reduced by as much as 5-fold at the time when germ cells attach onto Sertoli cells but preceding the establishment of specialized inter-Sertoli-germ cell junctions. Neither FSH nor 17␤-hydroxy-5␣-androstan-3-one was able to affect sertolin expression, whereas estradiol-17␤ and progesterone induced a significant increase in Sertoli cell sertolin expression in vitro. In addition, interleukin-1␣, a germ cell-derived cytokine, was also able to elicit a transient but significant increase in Sertoli cell sertolin expression. Sertolin expression was also shown to increase with testicular development and is likely to be associated with the onset of spermatogenesis. In addition, sertolin expression increased in the testis when generalized inflammation was induced in adult rats by injection of fermented yeast. These results show that sertolin will be useful in characterizing cell-cell interactions in the testis.Apart from the numerous morphological and molecular changes that take place in developing germ cells during spermatogenesis, these cells also migrate from the basal to the adluminal compartment, where fully developed spermatids are released into the tubular lumen at spermiation (1, 2). During the process of germ cell movement, it is envisioned that specialized inter-Sertoli and Sertoli-germ cell junctions must be intermittently disassembled and reassembled in a highly organized manner. As such, germ cell movement must consist of intermittent phases of junction disassembly and reassembly. These events probably also require the active participation of several proteases, protease inhibitors, junctional complex components, and signaling molecules that are found in the testis (3, 4). However, the intricate cascade(s) of events underlying spermatogenesis with respect to germ cell migration has not been elucidated. Recent studies from this laboratory have demonstrated that when germ cells consisting largely of spermatogonia and spermatocytes are cocultured with Sertoli cells in vitro for a short period of time prior to the establishment of specialized intercellular junctions, there are changes in the expression of several proteases, protease inhibitors (5, 6), and cell adhesion molecules (7) showing that germ cell attachment to Sertoli cells with the eventual establishment of specialized cell junctions consists of a series...

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Cells from Peripheral Tissues that Exhibit High APP Expression are Characterized by their High Membrane Fusion Activity

Cited by 23 publications

References 0 publications

Amyloid precursor protein in pancreatic islets

Amyloid precursor protein in pancreatic islets

An Integrative Omics Strategy to Assess the Germ Cell Secretome and to Decipher Sertoli-Germ Cell Crosstalk in the Mammalian Testis

Sertolin Is a Novel Gene Marker of Cell-Cell Interactions in the Rat Testis

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