Progressive neurologic dysfunctions 20 years after allogeneic bone marrow transplantation for Chediak-Higashi syndrome

Tardieu, Marc; Lacroix, Catherine; Neven, Bénédicte; Bordigoni, Pierre; Basile, Geneviève de Saint; Blanche, Stéphane; Fischer, Alain

doi:10.1182/blood-2005-01-0319

Cited by 114 publications

(85 citation statements)

References 14 publications

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“…Our results illustrating that Rab27, a gene linked to Griscelli syndrome, regulates synaptic transmission are consistent with recent findings from patients with ChediakHigashi syndrome, a disorder related to Griscelli syndrome (Tardieu et al, 2005). The authors found that after successful bone-marrow transplantation to treat the immunological defects, patients later develop severe neurological disorders in the absence of any structural damage that could have resulted from the disease.…”

Section: Molecular Biology Of the Cell 2622supporting

confidence: 81%

“…It is worth noting that other studies of Rab3A knockout mice have not observed alterations in either the readily releasable pool or in the numbers of docked or total synaptic vesicles at synapses (Schluter et al, 2004) and have argued that Rab3a acts at the fusion step rather than in earlier docking steps. Whether these differences represent synapse-type specific or organism specific differences will require a more detailed understanding of the mechanisms of Rab modulation of synaptic release.Our results illustrating that Rab27, a gene linked to Griscelli syndrome, regulates synaptic transmission are consistent with recent findings from patients with ChediakHigashi syndrome, a disorder related to Griscelli syndrome (Tardieu et al, 2005). The authors found that after successful bone-marrow transplantation to treat the immunological defects, patients later develop severe neurological disorders in the absence of any structural damage that could have resulted from the disease.…”

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confidence: 81%

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Regulation of Synaptic Transmission by RAB-3 and RAB-27 inCaenorhabditis elegans

Mahoney

Liu

Itoh

et al. 2006

MBoC

166

218

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Rab small GTPases are involved in the transport of vesicles between different membranous organelles. RAB-3 is an exocytic Rab that plays a modulatory role in synaptic transmission. Unexpectedly, mutations in the Caenorhabditis elegans RAB-3 exchange factor homologue, aex-3, cause a more severe synaptic transmission defect as well as a defecation defect not seen in rab-3 mutants. We hypothesized that AEX-3 may regulate a second Rab that regulates these processes with RAB-3. We found that AEX-3 regulates another exocytic Rab, RAB-27. Here, we show that C. elegans RAB-27 is localized to synapse-rich regions pan-neuronally and is also expressed in intestinal cells. We identify aex-6 alleles as containing mutations in rab-27. Interestingly, aex-6 mutants exhibit the same defecation defect as aex-3 mutants. aex-6; rab-3 double mutants have behavioral and pharmacological defects similar to aex-3 mutants. In addition, we demonstrate that RBF-1 (rabphilin) is an effector of RAB-27. Therefore, our work demonstrates that AEX-3 regulates both RAB-3 and RAB-27, that both RAB-3 and RAB-27 regulate synaptic transmission, and that RAB-27 potentially acts through its effector RBF-1 to promote soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) function. INTRODUCTIONNeurotransmitter release is accomplished by the fusion of neurotransmitter-filled synaptic vesicles at the presynaptic nerve terminal. This process occurs through a series of highly regulated steps that include synaptic vesicle transport, docking/tethering, priming, fusion, endocytosis, recycling, and neurotransmitter refilling (Sudhof, 2004). Several genes have been assigned roles in the various steps of the synaptic vesicle cycle. Rab3 (termed RAB-3 in Caenorhabditis elegans), a member of the Rab family of small GTPases, regulates synaptic transmission, possibly through the docking, priming, or fusion steps Schluter et al., 2004).Rabs act in a variety of cell types and regulate vesicular transport between organelles. Rabs cycle on and off membranes via a GTP-dependent mechanism (Zerial and McBride, 2001). Rab activity is regulated by two proteins, which act in an antagonistic manner. The guanine nucleotide exchange factor (GEF) exchanges GTP for GDP, and the GTPase activating protein activates the intrinsic GTPase activity of a Rab (Bernards, 2003). GDP bound Rabs are held off of the membrane by a GDP dissociation inhibitor (Wu et al., 1996). The GTP/membrane-bound form of Rabs typically binds to a variety of effectors that regulate particular steps of membrane transport and cell signaling (Zerial and McBride, 2001;Spang, 2004).Rab3 was once thought to play a central role in regulating release. However, recent work has shown that a quadruple knockout of all four isoforms of Rab3 in mice only results in a 30% reduction in evoked synaptic response (Schluter et al., 2004). This is consistent with work in C. elegans showing that mutations in the single rab-3 gene cause only mild defects in synaptic transmission . Surprisingly, more dramatic phe...

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Section: Molecular Biology Of the Cell 2622supporting

confidence: 81%

supporting

confidence: 81%

Regulation of Synaptic Transmission by RAB-3 and RAB-27 inCaenorhabditis elegans

Mahoney

Liu

Itoh

et al. 2006

MBoC

166

218

View full text Add to dashboard Cite

show abstract

“…9,10 ADA is known to be expressed systemically and other nonimmunologic deficits, including audiologic, hepatic, renal, and skeletal abnormalities, are well documented. [23][24][25][26] We also show that in addition to previously described motor neurologic defects, 27 children with Chédiak-Higashi syndrome have severe cognitive problems. The LYST protein defective in Chédiak-Higashi syndrome is ubiquitously expressed and is involved in controlling exocytosis of secretory granules, and its absence may therefore disturb neuronal lysosomal trafficking.…”

Section: Discussionmentioning

confidence: 58%

Cognitive and behavioral abnormalities in children after hematopoietic stem cell transplantation for severe congenital immunodeficiencies

Titman

Pink

Skucek

et al. 2008

Blood

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“…In addition, Rab27a seems not to be expressed in the brain. 36 Hence, in contrast to what has been shown in Chediak-Higashi syndrome with central nervous HLH as well as progressive neurologic disease, 37 which, at least in the mouse model, seems to be correlated with a degenerative loss of Purkinje cells, 38 neurologic symptoms in GS2 patients probably result uniquely from HLH-related sequelae that predate the HSCT and thus underline the benefit of early transplantation in GS2. Two of our patients (siblings P4 and P7) suffered from pre-HSCT neuropathy that involved the peripheral nerves and (in one of them) the spinal nerve roots.…”

Section: Discussionmentioning

confidence: 88%

Hematopoietic stem cell transplantation in Griscelli syndrome type 2: a single-center report on 10 patients

Schmid

Moshous

Boddaert

et al. 2009

Blood

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Progressive neurologic dysfunctions 20 years after allogeneic bone marrow transplantation for Chediak-Higashi syndrome

Cited by 114 publications

References 14 publications

Regulation of Synaptic Transmission by RAB-3 and RAB-27 inCaenorhabditis elegans

Regulation of Synaptic Transmission by RAB-3 and RAB-27 inCaenorhabditis elegans

Cognitive and behavioral abnormalities in children after hematopoietic stem cell transplantation for severe congenital immunodeficiencies

Hematopoietic stem cell transplantation in Griscelli syndrome type 2: a single-center report on 10 patients

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