Expression of a glycosyl phosphatidylinositol-anchored adhesion molecule, the glycoprotein F3, in the adult rat hypothalamo-neurohypophysial system

doi:10.1016/0006-8993(95)00555-5

Brain Research

Volume 689, Issue 2, 21 August 1995, Pages 271-280

https://doi.org/10.1016/0006-8993(95)00555-5 Get rights and content

Abstract

The F3 cell surface glycoprotein consists of six immunoglobulin-like domains, four fibronectin type III repeats and a glycosyl-phosphatidylinositol anchor and is found in membrane-bound and soluble form. Until now, it has been localized mainly on axons of subsets of developing and postnatal neurons and has been implicated in axonal growth and synaptogenesis. We here examined its expression in the adult rat hypothalamo-neurohypophysial system composed of magnocellular neurons whose axons can undergo remodelling in adulthood in response to lesion or physiological stimulation. Immunoblot analyses demonstrated high levels of F3 immunoreactivity in the hypothalamic nuclei containing the somata of the neurons, in the median eminence, through which pass their axons and in the neurohypophysis, where they terminate. The amount of F3 detected in the latter was 2-fold that in the hypothalamus. In addition, soluble forms predominated in the neurohypophysis and GPI-linked forms in the hypothalamus. Immuncytochemistry revealed a strong F3 immunoreactivity throughout the neurohypophysis and internal layer of the median eminence, characterized by a punctate labeling of fibers and dense filling of dilatations. In the hypothalamic nuclei, staining of variable intensity was visible in the cytoplasm of some magnocellular somata. In contrast, in colchicine-treated rats, all magnocellular somata throughout the hypothalamus displayed intense labeling while staining in the neurohypophysis was greatly reduced. Our observations reveal that neurons of the adult hypothalamo-neurohypophysial system express high level of F3, even under normal conditions. In view of its distribution and the differing proportions of membrane-bound and soluble forms, we propose that, after synthesis in the hypothalamus, F3 is targeted to the neurohypophysis where it accumulates in neurosecretory terminals or is released into the extracellular space. It remains to be seen whether its expression is linked to the secretion of the neurohypophysial peptides and in particular, to the ability of these neurons to undergo structural remodelling in adulthood.

Reference (38)

BlochR.J.
Cell to cell interactions during synaptogenesis
Curr. Opin. Cell Biol.
(1989)
BonfantiL. et al.
Mapping of the distribution of polysialylated neural cell adhesion molecule throughout the central nervous system of the adult rat, an immunohistochemical study
Neuroscience
(1992)
CraigA. et al.
Neuronal polarity
Curr. Opin. Neurobiol.
(1992)
DottiC.G. et al.
Polarized sorting of viral glycoproteins to the axons and dendrites of hippocampal neurons
Cell
(1990)
FurleyA.J. et al.
The axonal glycoprotein TAG-1 is an immunoglobulin superfamily member with neurite outgrowth promoting activity
Cell
(1990)
GennariniG. et al.
Transfected F3/F11 neuronal cell surface protein mediates intercellular adhesion and promotes neurite outgrowth
Neuron
(1991)
KissJ.Z. et al.
Nerve dependent expression of high polysialic acid neural cell adhesion molecule in neurohypophyseal astrocytes of adult rats
Neuroscience
(1993)
LisantiM.P. et al.
Glycophospholipid membrane anchoring provides clues to the mechanism of protein sorting in polarized epithelial cells
Trends Biochem. Sci.
(1990)
LowM.G.
The glycosyl-phosphatidylinositol anchor of membrane proteins
Biochim. Biophys. Acta
(1989)
PeshevaP. et al.
The F3/F11 cell adhesion molecule mediates the repulsion of neurons by the extracellular matrix glycoprotein J1-160/180
Neuron
(1993)

TheodosisD.T. et al.

Activity-dependent neuronal-glial and synaptic plasticity in the adult mammalian hypothalamus

Neuroscience

(1993)

YoshiharaY. et al.

BIG-1: a new TAG-1/F3-related member of the immunoglobulin super-family with neurite outgrowth-promoting activity

Neuron

(1994)

BrownsteinM.J. et al.

Synthesis, transport and release of posterior pituitary hormones

Science

(1980)

BrümmendorfT. et al.

The axonal recognition molecule F11 is a multifonctional protein: specific domains mediate interactions with Ng-CAM and restrictin

Neuron

(1993)

BrümmendorfT. et al.

Neural cell adhesion molecule F11: homology with fibronectin type III and immunoglobulin type C domains

Neuron

(1988)

DellmanH.D.

Degeneration and regeneration of neurosecretory systems

Int. Rev. Cytol.

(1973)

DottiC.G. et al.

Polarized sorting of glypiated proteins in hippocampal neurons

Nature (London)

(1991)

DoeringJ.L. et al.

Biosynthesis of glycophosphatidylinositol membrane anchors

J. Biol. Chem.

(1990)

DurbecP. et al.

A soluble form of F3 neuronal cell adhesion molecule promotes neurite outgrowth

J. Cell Biol.

(1992)

Cited by (30)

The prion-like spreading of α-synuclein: From in vitro to in vivo models of Parkinson's disease
2019, Ageing Research Reviews
Citation Excerpt :
α-Syn is known to directly interact with lipids or proteins at the plasma membrane, which could facilitate its entering in a non-specific way (Auluck et al., 2010). Several studies have shown that α-syn associates to lipid rafts, and more specifically to the glycolipid, ganglioside GM1, which is abundantly expressed in the brain (Fortin et al., 2004; Olive et al., 1995). Whether and how this interaction could lead to α-syn internalization is not clear yet.
Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease. PD is characterized by the loss of dopaminergic neurons, primarily in brain regions that control motor functions, thereby leading to motor impairments in the patients. Pathological aggregated forms of the synaptic protein, α-synuclein (α-syn), are involved in the generation and progression of PD. In PD brains, α-syn accumulates inside neurons and propagates from cell-to-cell in a prion-like manner. In this review, we discuss the in vitro and in vivo models used to study the prion-like properties of α-syn and related findings. In particular, we focus on the different mechanisms of α-syn spreading, which could be relevant for the development of alternative therapeutic approaches for PD treatment.
Distribution of osmoregulatory peptides and neuronal-glial configuration in the hypothalamic magnocellular nuclei of desert rodents
2011, Comptes Rendus - Biologies
Citation Excerpt :
These tissues were prepared further for electron microscopy. For single immunolabeling, standard immunofluorescence and immunoperoxidase techniques were performed on free-floating sections of brains according to procedures described in detail in earlier studies [12–14]. Briefly, after rinsing in Tris-buffered saline (TBS), sections were treated with casein (0.5% in PBS) for 1 hr to block non-specific sites.
The desert rodents Psammomys obesus and Gerbillus tarabuli live under extreme conditions and overcome food and water shortage by modes of food and fluid intake specific to each species. Using immunohistochemistry and electron microscopy, we found that the hypothalamic magnocellular nuclei, and in particular, their vasopressinergic component, is highly and similarly developed in Psammomys and Gerbillus. In comparison to other rodents, the hypothalamus in both species contains more magnocellular VP neurons that, together with oxytocin neurons, accumulate in distinct and extensive nuclei. As in dehydrated rodents, many magnocellular neurons contained both neuropeptides. A striking feature of the hypothalamic magnocellular system of Psammomys and Gerbillus was its display of ultrastructural properties related to heightened neurosecretion, namely, a significant reduction in glial coverage of neuronal somata and dendrites in the hypothalamic nuclei. There were many neuronal elements whose surfaces were directly juxtaposed and shared the same synapses. Their magnocellular nuclei also showed a high level of sialylated isoform of the Neural Cell Adhesion Molecule (PSA-NCAM) that underlies their capacity for neuronal and glial plasticity. These species thus offer striking models of structural neuronal and glial plasticity linked to natural conditions of heightened neurosecretion.
Deciphering the mechanisms of homeostatic plasticity in the hypothalamo-neurohypophyseal system - Genomic and gene transfer strategies
2004, Progress in Biophysics and Molecular Biology
The hypothalamo-neurohypophyseal system (HNS) is the specialised brain neurosecretory apparatus responsible for the production of a peptide hormone, vasopressin, that maintains water balance by promoting water conservation at the level of the kidney. Dehydration evokes a massive increase in the regulated release of hormone from the HNS, and this is accompanied by a plethora of changes in morphology, electrical properties and biosynthetic and secretory activity, all of which are thought to facilitate hormone production and delivery, and hence the survival of the organism. We have adopted a functional genomic strategy to understand the activity dependent plasticity of the HNS in terms of the co-ordinated action of cellular and genetic networks. Firstly, using microarray gene-profiling technologies, we are elucidating which genes are expressed in the HNS, and how the pattern of expression changes following physiological challenge. The next step is to use transgenic rats to probe the functions of these genes in the context of the physiological integrity of the whole organism.
Dynamic neuronal-glial interactions: An overview 20 years later
2004, Peptides
After commenting on some perceived reasons why our review may have been relatively frequently cited, a brief overview is presented that first summarizes what we knew 25 years ago about the dynamic neuronal–astroglial interactions that occur in response to changes in the physiological state of the animal. The brain system in which these dynamic interactions were studied was the magnocellular hypothalamo-neurohypophysial system (mHNS) of the rat. The mHNS developed as and continues to be the model system yielding the most coherent picture of dynamic morphological changes and insights into their functional consequences. Many other brain areas, however, have more recently come under scrutiny in the search for glial–neuronal dynamisms. Outlined next are some of the questions concerning this phenomenon that led to the research efforts immediately following the initial discoveries, along with the answers, both complete and incomplete, obtained to those research questions. The basis for this first wave of follow-up research can be characterized by the phrase “what we knew we didn’t know at that time.” The final section is an update and brief overview of highlights of both “what we know now” and “what we now know that we don’t know” about dynamic neuronal–astroglial interactions in the mHNS.
Chondroitin sulfate proteoglycan phosphacan/RPTPβ in the hypothalamic magnocellular nuclei
2002, Brain Research
Citation Excerpt :
NCAM containing polysialic acid (PSA) is still expressed in the HNS of adult rats, although its expression is abundant throughout the late embryonic and early postnatal brain and is replaced by adult isoforms containing less than 10% PSA [17,43,47]. High levels of expression of F3 [31,36] and L1 [8] have also been demonstrated in the adult HNS. Recently, we demonstrated that OBCAM and Kilon, which consist of three immunoglobulin (IgG)-like domains, are dendrite-associated CAMs in AVP-secreting magnocellular neurons [27].
The hypothalamo–neurohypophysial system synthesizes and releases arginine vasopressin (AVP) and oxytocin (OXT) with physiological stimulation. In the present study, we investigated localization of a chondroitin sulfate proteoglycan (CSPG), phosphacan/RPTPβ, in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of adult rats at both the light and electron microscopic levels. Immunohistochemical analyses demonstrated stronger phosphacan/RPTPβ immunoreactivity within the SON and PVN compared with adjacent hypothalamic areas. Double labeling experiments showed phosphacan/RPTPβ immunoreactivity constituting punctate networks to surround the somata and dendrites of AVP- and OXT-secreting magnocellular neurons. Electron microscopic examination further revealed strong phosphacan/RPTPβ immunoreactivity at extracellular membrane surface of some axons, somata, and dendrites of the SON, but not of synaptic junctions. Interestingly, phosphacan/RPTPβ immunoreactivity was also observed at extracellular surface membrane between astrocytic processes and neurons rather than between magnocellular neurons. The present results indicate the high expression of the CSPG, phosphacan/RPTPβ at the extracellular space in the hypothalamic AVP- and OXT-secreting magnocellular neurons.
Expression of high levels of tubulin and microtubule-associated protein 2d in the neurohypophysial astrocytes of adult rat
2002, Neuroscience
The hypothalamo-neurohypophysial system, containing arginine vasopressin and oxytocin, is well known to show reversible morphological reorganization for both neurons and glial cells during chronic physiological stimulation. To determine the molecular background for these morphological changes, we investigated the expression of tubulin and microtubule-associated protein (MAP) 2d in the neurohypophysial astrocytes, pituicytes of adult rats by using reverse transcription-polymerase chain reaction, western blot, and immunohistochemistry. The mRNA of MAP2d was expressed at higher levels than that of MAP2c in the neurohypophysis, cerebral cortex, and cerebellum. In contrast, predominant expression of mRNA of MAP2c was detected in the olfactory bulb. Western blot analysis showed the presence of MAP2d in the neurohypophysis, however the amount was below the detection level in the cerebral cortex and cerebellum. A double labeling study using a confocal laser scanning microscope showed intense tubulin immunoreactivity in the glial fibrillary acidic protein (GFAP)-positive pituicytes of the intact neurohypophysis. Almost no tubulin immunoreactivity was observed in the astrocytes of the intact cerebral cortex, cerebellum, and supraoptic nucleus, in contrast to strong tubulin immunoreactivity in neuronal dendrites and somata. Interestingly, intense tubulin immunoreactivity was also observed in the GFAP-positive reactive astrocytes in the immediate vicinity of the artificial lesion of the cerebral cortex. Electron microscopic observation further demonstrated the presence of a lot of microtubules in the pituicytes of intact rats.
The present results demonstrate that pituicytes in the adult rat neurohypophysis expresses high levels of tubulin and MAP2d compared with normal brain astrocytes, and suggest that the ability of astrocytic morphological alteration may be at least partly ascribed to this high expression of microtubule proteins.

View all citing articles on Scopus

View full text

Expression of a glycosyl phosphatidylinositol-anchored adhesion molecule, the glycoprotein F3, in the adult rat hypothalamo-neurohypophysial system

Abstract

Curr. Opin. Cell Biol.

Neuroscience

Curr. Opin. Neurobiol.

Cell

Cell

Neuron

Neuroscience

Trends Biochem. Sci.

Biochim. Biophys. Acta

Neuron

Neuroscience

Neuron

Synthesis, transport and release of posterior pituitary hormones

Science

The axonal recognition molecule F11 is a multifonctional protein: specific domains mediate interactions with Ng-CAM and restrictin

Neuron

Neural cell adhesion molecule F11: homology with fibronectin type III and immunoglobulin type C domains

Neuron

Degeneration and regeneration of neurosecretory systems

Int. Rev. Cytol.

Polarized sorting of glypiated proteins in hippocampal neurons

Nature (London)

Biosynthesis of glycophosphatidylinositol membrane anchors

J. Biol. Chem.

A soluble form of F3 neuronal cell adhesion molecule promotes neurite outgrowth

J. Cell Biol.