Immunocytochemical localization of a neuron-specific thrombospondin-1-like protein, NELL2: light and electron microscopic studies in the rat brain

Oyasu, Miho; Kuroda, Shinya; Nakashita, Mayumi; Fujimiya, Mineko; Kikkawa, Ushio; Saito, Naoaki

doi:10.1016/s0169-328x(99)00342-3

Cited by 44 publications

(55 citation statements)

References 20 publications

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“…However, N-terminal EGFP-tagged NELL2 (EGFP-NELL2) did not exhibit an expression pattern typical of NELL2, which is expressed in the trans-Golgi network and shows an increased molecular weight. These results are consistent with previous studies that predicted structural features such as a cleavable signal peptide and N-glycosylation of the protein (Nelson et al, 2004;Oyasu et al, 2000). One of the most prominent characteristics of NELL2 is its speed and anterograde movement.…”

Section: Discussionsupporting

confidence: 93%

“…Two human and rat cDNAs were later isolated as NELL1 and NELL2 (nel-like genes), with 50% and 80% homology to nel Luce and Burrows, 1999;Watanabe et al, 1996). Neural tissue-specific expression of NELL2 has been reported in developing and post-natal rats (Kim et al, 2002;Nelson et al, 2004;Oyasu et al, 2000) and humans (Watanabe et al, 1996). NELL2 mRNA is predominantly expressed in the central nervous system throughout the pre-natal stages, and its expression gradually increases during embryonic development.…”

Section: Introductionmentioning

confidence: 99%

“…NELL2 mRNA is predominantly expressed in the central nervous system throughout the pre-natal stages, and its expression gradually increases during embryonic development. In the adult rat brain, high levels of NELL2 mRNA are detected in the taenia tecta, piriform cortex, hippocampus, dentate gyrus, cerebellar cortex, ambiguous nucleus, and inferior olivary nucleus (Kim et al, 2002;Oyasu et al, 2000). In addition, NELL2 is an estrogen-induced gene in the adult female rat hypothalamus and is involved in the estrogendependent organization of the sexually dimorphic nucleus in the preoptic area (Jeong et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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The Molecular Mechanism of NELL2 Movement and Secretion in Hippocampal Progenitor HiB5 Cells

Hwang

Kim

et al. 2013

Molecules and Cells

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Neural epidermal growth factor-like protein-like 2 (NELL2) is a secreted glycoprotein that is predominantly expressed in the nervous system, but little is known about the intracellular movement and secretion mechanism of this protein. By monitoring the localization and movements of enhanced green fluorescent protein (EGFP)-labeled NELL2 in living cultured hippocampal neuroprogenitor HiB5 cells, we determined the subcellular localization of NELL2 and its intracellular movement and secretion mechanism. Cterminal EGFP-fused NELL2 showed a typical expression pattern of secreted proteins, especially with respect to its localization in the endoplasmic reticulum, Golgi apparatus, and punctate structures. Vesicles containing NELL2 exhibited bidirectional movement in HiB5 cells. The majority of the vesicles (70.1%) moved in an anterograde direction with an average velocity of 0.454 μm/s, whereas some vesicles (28.7%) showed retrograde movement with an average velocity of 0.302 μm/s. The movement patterns of NELL2 vesicles were dependent upon the presence of microtubules in HiB5 cells. Anterograde movement of NELL2 did not lead to a detectable accumulation of NELL2 in the peripheral region of the cell, indicating that it was secreted into the culture medium. We also showed that the N-terminal 29 amino acids of NELL2 were important for secretion of this protein. Taken together, these results strongly suggest that the N-terminal region of NELL2 determines both the pattern of its intracellular expression and transport of NELL2 vesicles by high-velocity movement. Therefore, NELL2 may affect the cellular activity of cells in a paracrine or autocrine manner.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Molecular Mechanism of NELL2 Movement and Secretion in Hippocampal Progenitor HiB5 Cells

Hwang

Kim

et al. 2013

Molecules and Cells

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“…Subsequently two Nel-like proteins, NELL1 and NELL2, were isolated from a human fetal brain library (Watanabe et al, 1996). Of these two mammalian NEL proteins, NELL2 appears to be the mammalian counterpart to chick Nel (Kuroda et al, 1999;Oyasu et al, 2000), because, like Nel, NELL2 is almost exclusively expressed in neurons (Oyasu et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

“…Because NELL2 is ubiquitously expressed in neurons, it was considered to play general roles in maintaining neuronal functions (Kim et al, 2002;Oyasu et al, 2000). However, we recently found that NELL2 is specifically expressed in glutamatergic neurons, but not in the gonadotropin-releasing hormone (GnRH) neurons of the rat hypothalamus (Ha et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Regulation of the Female Rat Estrous Cycle by a Neural Cell-Specific Epidermal Growth Factor-like Repeat Domain Containing Protein, NELL2

Ryu

Kim

Jeong

et al. 2011

Molecules and Cells

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NELL2, a protein containing epidermal growth factor-like repeat domains, is predominantly expressed in the nervous system. In the mammalian brain, NELL2 expression is mostly neuronal. Previously we found that NELL2 is involved in the onset of female puberty by regulating the release of gonadotropin-releasing hormone (GnRH), and in normal male sexual behavior by controlling the development of the sexually dimorphic nucleus of the preoptic area (POA). In this study we investigated the effect of NELL2 on the female rat estrous cycle. NELL2 expression in the POA was highest during the proestrous phase. NELL2 mRNA levels in the POA were increased by estrogen treatment in ovariectomized female rats. Blocking NELL2 synthesis in the female rat hypothalamus decreased the expression of kisspeptin 1, an important regulator of the GnRH neuronal apparatus, and resulted in disruption of the estrous cycle at the diestrous phase. These results indicate that NELL2 is involved in the maintenance of the normal female reproductive cycle in mammals.

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Haploinsufficiency ofANO6, NELL2andDBX2in a boy with intellectual disability and growth delay

Carlsen

Frengen

Fannemel

et al. 2015

American J of Med Genetics Pt A

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We report on a 10-year-old-boy presenting with moderate intellectual disability (ID), impaired motor skills, hypotonia, growth delay, minor anomalies, misaligned teeth, pectus excavatum, small hands and feet, widely spaced nipples, and a 1.13 Mb de novo deletion on HSA12q12 (chr12:44,830,147-45,964,945 bp, hg19), deleting ANO6, NELL2, and DBX2 and the pseudogenes PLEKHA8P1 and RACGAP1P. We suggest DBX2 and NELL2 as disease-causing genes and their haploinsufficiency to be involved in the psychomotor delay in the patient. DBX2 encodes a homeobox protein, highly expressed during neuronal development and regulating differentiation of interneurons in brain and spinal cord. NELL2 is expressed in most of the central and peripheral nervous system, with highest expression in hippocampus and cerebellum, maximizing during neuronal differentiation. The deletion in our patient is the smallest in HSA12q12 reported to date, and it is included in the deletion carried by four previously reported patients. The clinical presentation of these patients points to the recurrence of the following manifestation, possibly delineating a 12q12 deletion syndrome phenotype: moderate to severe developmental/intellectual delay, hypotonia, postnatal growth retardation, skeletal and dental anomalies, minor facial anomalies including strabismus, down slanting palpebral fissures, and large/low-set ears.

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Immunocytochemical localization of a neuron-specific thrombospondin-1-like protein, NELL2: light and electron microscopic studies in the rat brain

Cited by 44 publications

References 20 publications

The Molecular Mechanism of NELL2 Movement and Secretion in Hippocampal Progenitor HiB5 Cells

The Molecular Mechanism of NELL2 Movement and Secretion in Hippocampal Progenitor HiB5 Cells

Regulation of the Female Rat Estrous Cycle by a Neural Cell-Specific Epidermal Growth Factor-like Repeat Domain Containing Protein, NELL2

Haploinsufficiency ofANO6, NELL2andDBX2in a boy with intellectual disability and growth delay

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