A human gene similar to Drosophila melanogaster peanut maps to the DiGeorge syndrome region of 22q11

McKie, J; Sutherland, Helen; Harvey, Emma L.; Kim, Ung-Jin; Scambler, Peter J.

doi:10.1007/s004390050576

Cited by 32 publications

(14 citation statements)

References 40 publications

(44 reference statements)

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“…This is surprising given the number of linkages of CDCrel-1 to disease and neuronal function. First, CDCrel-1 had been identified within the locus that is commonly deleted in patients with DiGeorge syndrome (28). In these individuals, haploinsuffi- FIG.…”

Section: Discussionmentioning

confidence: 99%

“…In the first study, CDCrel-1 was found as the upstream part of a fusion transcript containing the ␤-subunit of the glycoprotein 1b platelet receptor (43) due to its nonconsensus polyadenylation sequence. As well, CDCrel-1 was identified as a gene within the segment of chromosome 22q11.2 that is commonly deleted in velo-cardiofacial and DiGeorge syndromes in humans (28). The latter is a complex congenital disorder including parathyroid and thymic hypoplasia as well as defects of the heart, which results, in part, in impaired migration of neural crest cells into the pharyngeal arches and pouches.…”

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confidence: 99%

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The Septin CDCrel-1 Is Dispensable for Normal Development and Neurotransmitter Release

Peng

Jia

Zhang

et al. 2002

Molecular and Cellular Biology

110

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Septins are GTPases required for the completion of cytokinesis in a variety of organisms, yet their role in this process is not known. Septins may have additional functions since the mammalian septin CDCrel-1 is predominantly expressed in the nervous system, a largely postmitotic tissue. While relatively little is known about the function of this protein, we have previously shown that it is involved in regulated secretion. In addition, the gene encoding this protein maps to a locus often deleted in velo-cardiofacial and DiGeorge syndromes, and CDCrel-1 has recently been shown to be a direct target of the E3 ubiquitin ligase activity of Parkin, a causative agent in autosomal recessive forms of Parkinson's disease. Here we show that CDCrel-1 expression rises at the time of synaptic maturation and that CDCrel-1 is present in a complex that includes the septins Nedd5 and CDC10. To investigate its function in the nervous system, we generated homozygotic CDCrel-1 null mice and showed that these mice appear normal with respect to synaptic properties and hippocampal neuron growth in vitro. Moreover, we found that while the expression of a number of synaptic proteins is not affected in the CDCrel-1 mutant mice, the expression of other septins is altered. Together, these data suggest that CDCrel-1 is not essential for neuronal development or function, and that changes in expression of other septins may account for its functional redundancy.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

The Septin CDCrel-1 Is Dispensable for Normal Development and Neurotransmitter Release

Peng

Jia

Zhang

et al. 2002

Molecular and Cellular Biology

110

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“…However, this choice would prove later to be less than perfect, because we observed the highest levels of CDCrel-1 mRNA in organs and cells no longer undergoing active cell division, namely brain, heart, and megakaryocytes (6). CDCrel-1 also has been referred to as PNUT-like based on its similarity to the well characterized Drosophila septin (7,8).…”

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confidence: 99%

A prototypic platelet septin and its participation in secretion

Dent

Kato

Peng

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

118

132

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Studies are presented characterizing platelet CDCrel-1, a protein expressed to high levels by megakaryocytes and belonging to a family of conserved proteins, termed septin. Septin filaments originally were identified in yeast as essential for budding but have become increasingly associated with processes in higher eukaryotic cells involving active membrane movement such as cytokinesis and vesicle trafficking. Direct proof of an in vivo function for septins in higher eukaryotes is limited to the characterization of the Drosophila septin, termed PNUT. We present studies identifying platelet CDCrel-1 as a protein kinase substrate in the presence of known platelet agonists. The immunopurification of CDCrel-1 revealed it to be part of a macromolecular complex containing a protein involved in platelet secretion, syntaxin 4. Moreover, CDCrel-1 was localized in situ to areas surrounding platelet-storage granules. The relevance of CDCrel-1 to normal platelet function was established with the characterization of platelets from a CDCrel-1 Null mouse. As compared with platelets from wild-type littermates, CDCrel-1 Null platelets aggregate and release stored [ 14 C]serotonin in the presence of subthreshold levels of collagen. These results provide new insights into the mechanisms regulating platelet secretion and identify platelet septins as a protein family contributing to membrane trafficking within the megakaryocyte and platelet.

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“…To date, nine septin genes have been identified in mammalian genomes: Diff6 (Nottenburg et al, 1990), H5 (Kato, 1990), CDC10 (Nakatsuru et al, 1994), Nedd5/KIAA0158 (Kumar et al, 1992;Nagase et al, 1995;Kinoshita et al, 1997), CDCrel-1/PNUTL1 (McKie et al, 1997;Zieger et al, 1997), KIAA0128/Septin6 (Nagase et al, 1995), KIAA0202 (Nagase et al,1996), E-septin/KIAA0991 (Fung and Scheller, 1999;Nagase et al, 1999), and G-septin (Xue et al, 2000). Nedd5, CDC10, Diff6, and Septin6 colocalize near the contractile ring during cytokinesis in human cells, and microinjection of anti-Nedd5 antibodies interferes with cytokinesis of cultured cells, suggesting that septins play important roles in cytokinesis in mammalian cells (Kinoshita et al, 1997;unpublished observations).…”

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confidence: 99%

Differential localization of septins in the mouse brain

2000

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We have carried out a comparative immunohistochemical study on four members of the septin family, CDCrel-1, Septin6, CDC10, and H5, which are abundantly expressed in the adult mouse brain. We found that each septin showed overlapping but distinct distribution at the levels of light and electron microscopy. CDCrel-1 was abundant in inhibitory presynaptic terminals and associated with GABAergic vesicles in the thalamus, globus pallidus, and cerebellar nuclei. Septin6 was associated with synaptic vesicles in various brain regions, including glomeruli of the olfactory bulb. CDC10 was diffusely expressed in the brain and was localized beneath presynaptic membrane and astroglial processes. H5 was localized in the astroglial processes in some specific brain regions. The differential expression and subcellular localization of these septins indicates that a given neuron or glial cell expresses a specific set of septin monomers and that the resulting septin complexes with distinct compositions may play distinct roles in the brain.

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A human gene similar to Drosophila melanogaster peanut maps to the DiGeorge syndrome region of 22q11

Cited by 32 publications

References 40 publications

The Septin CDCrel-1 Is Dispensable for Normal Development and Neurotransmitter Release

The Septin CDCrel-1 Is Dispensable for Normal Development and Neurotransmitter Release

A prototypic platelet septin and its participation in secretion

Differential localization of septins in the mouse brain

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