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Matricellular proteins of the Cyr61/CTGF/NOV (CCN) family and the nervous system.

Malik AR, Liszewska E, Jaworski J - Front Cell Neurosci (2015)

Bottom Line: CCN proteins also influence the activity of growth factors and cytokines and integrate their activity with integrin signaling.Thus, the major aim of this review is to introduce the CCN protein family to the neuroscience community.We first discuss the structure, interactions, and cellular functions of CCN proteins and then provide a detailed review of the available data on the neuronal expression and contribution of CCN proteins to nervous system development, function, and pathology.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology Warsaw, Poland.

ABSTRACT
Matricellular proteins are secreted proteins that exist at the border of cells and the extracellular matrix (ECM). However, instead of playing a role in structural integrity of the ECM, these proteins, that act as modulators of various surface receptors, have a regulatory function and instruct a multitude of cellular responses. Among matricellular proteins are members of the Cyr61/CTGF/NOV (CCN) protein family. These proteins exert their activity by binding directly to integrins and heparan sulfate proteoglycans and activating multiple intracellular signaling pathways. CCN proteins also influence the activity of growth factors and cytokines and integrate their activity with integrin signaling. At the cellular level, CCN proteins regulate gene expression and cell survival, proliferation, differentiation, senescence, adhesion, and migration. To date, CCN proteins have been extensively studied in the context of osteo- and chondrogenesis, angiogenesis, and carcinogenesis, but the expression of these proteins is also observed in a variety of tissues. The role of CCN proteins in the nervous system has not been systematically studied or described. Thus, the major aim of this review is to introduce the CCN protein family to the neuroscience community. We first discuss the structure, interactions, and cellular functions of CCN proteins and then provide a detailed review of the available data on the neuronal expression and contribution of CCN proteins to nervous system development, function, and pathology.

No MeSH data available.


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CCN protein abundance in the selected human brain regions according to the Human Protein Atlas (HPA).
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Figure 4: CCN protein abundance in the selected human brain regions according to the Human Protein Atlas (HPA).

Mentions: CCN1 mRNA has been detected in different areas of the developing and adult human and rat brain and in rat hippocampal and cortical neurons cultured in vitro (Albrecht et al., 2000; Malik et al., 2013). Interestingly, CCN1 mRNA levels in the rat hippocampus were higher during embryonic development and dropped postnatally, suggesting that this protein may play an important role during embryonic brain development (Malik et al., 2013). A similar developmental trend in CCN1 expression was observed in cultured hippocampal neurons (Malik et al., 2013). An analysis of ABA data showed fluctuations of CCN1 mRNA amount in embryonic brain but confirmed higher CCN1 mRNA levels in the mouse embryonic day 18 (E18) brain compared with early postnatal weeks. The ABA suggests partial expression recovery in the cortex from postnatal day 28 (P28) onward (Figure 2). In the adult brain (P56) the ABA provides evidence for CCN1 mRNA in deeper cortical layers (Figure 3). BrainStars* provides evidence of CCN1 mRNA in the adult mouse CNS, with the highest levels in the retina. In the adult human brain, CCN1 mRNA was detected throughout the CNS, with the strongest expression in the spinal cord, frontal, temporal, and occipital cortices, hippocampus, and caudate nucleus (Albrecht et al., 2000). This observation appears to be confirmed by the HPA, in which mild CCN1 protein levels were present in the cortex and hippocampus, but the highest levels were detected in the cerebellum (Figure 4). An analysis of the cell specificity of immunohistochemical signal showed that CCN1 protein can be detected mostly in neurons, whereas its expression in glia is lower or undetectable (Table 3).


Matricellular proteins of the Cyr61/CTGF/NOV (CCN) family and the nervous system.

Malik AR, Liszewska E, Jaworski J - Front Cell Neurosci (2015)

CCN protein abundance in the selected human brain regions according to the Human Protein Atlas (HPA).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4478388&req=5

Figure 4: CCN protein abundance in the selected human brain regions according to the Human Protein Atlas (HPA).
Mentions: CCN1 mRNA has been detected in different areas of the developing and adult human and rat brain and in rat hippocampal and cortical neurons cultured in vitro (Albrecht et al., 2000; Malik et al., 2013). Interestingly, CCN1 mRNA levels in the rat hippocampus were higher during embryonic development and dropped postnatally, suggesting that this protein may play an important role during embryonic brain development (Malik et al., 2013). A similar developmental trend in CCN1 expression was observed in cultured hippocampal neurons (Malik et al., 2013). An analysis of ABA data showed fluctuations of CCN1 mRNA amount in embryonic brain but confirmed higher CCN1 mRNA levels in the mouse embryonic day 18 (E18) brain compared with early postnatal weeks. The ABA suggests partial expression recovery in the cortex from postnatal day 28 (P28) onward (Figure 2). In the adult brain (P56) the ABA provides evidence for CCN1 mRNA in deeper cortical layers (Figure 3). BrainStars* provides evidence of CCN1 mRNA in the adult mouse CNS, with the highest levels in the retina. In the adult human brain, CCN1 mRNA was detected throughout the CNS, with the strongest expression in the spinal cord, frontal, temporal, and occipital cortices, hippocampus, and caudate nucleus (Albrecht et al., 2000). This observation appears to be confirmed by the HPA, in which mild CCN1 protein levels were present in the cortex and hippocampus, but the highest levels were detected in the cerebellum (Figure 4). An analysis of the cell specificity of immunohistochemical signal showed that CCN1 protein can be detected mostly in neurons, whereas its expression in glia is lower or undetectable (Table 3).

Bottom Line: CCN proteins also influence the activity of growth factors and cytokines and integrate their activity with integrin signaling.Thus, the major aim of this review is to introduce the CCN protein family to the neuroscience community.We first discuss the structure, interactions, and cellular functions of CCN proteins and then provide a detailed review of the available data on the neuronal expression and contribution of CCN proteins to nervous system development, function, and pathology.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology Warsaw, Poland.

ABSTRACT
Matricellular proteins are secreted proteins that exist at the border of cells and the extracellular matrix (ECM). However, instead of playing a role in structural integrity of the ECM, these proteins, that act as modulators of various surface receptors, have a regulatory function and instruct a multitude of cellular responses. Among matricellular proteins are members of the Cyr61/CTGF/NOV (CCN) protein family. These proteins exert their activity by binding directly to integrins and heparan sulfate proteoglycans and activating multiple intracellular signaling pathways. CCN proteins also influence the activity of growth factors and cytokines and integrate their activity with integrin signaling. At the cellular level, CCN proteins regulate gene expression and cell survival, proliferation, differentiation, senescence, adhesion, and migration. To date, CCN proteins have been extensively studied in the context of osteo- and chondrogenesis, angiogenesis, and carcinogenesis, but the expression of these proteins is also observed in a variety of tissues. The role of CCN proteins in the nervous system has not been systematically studied or described. Thus, the major aim of this review is to introduce the CCN protein family to the neuroscience community. We first discuss the structure, interactions, and cellular functions of CCN proteins and then provide a detailed review of the available data on the neuronal expression and contribution of CCN proteins to nervous system development, function, and pathology.

No MeSH data available.


Related in: MedlinePlus