Cednik

Hsu, Tina; Coughlin, Carrie C.; Monaghan, Kristin G.; Fiala, Elise; McKinstry, Robert C.; Paciorkowski, Alex R.; Shinawi, Marwan

doi:10.1177/2329048x17733214

Cited by 16 publications

(12 citation statements)

References 13 publications

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“…The Qbc-SNARE SNAP29 has previously also been ascribed a role in Golgi morphology, and its dysfunction could likely result in glycosylation defects [200]. Of note, several missense and truncating mutations in SNAP29 have been associated with cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma syndrome (CEDNIK, a disorder of brain development, facial dysmorphism, and skin), and Pelizaeus-Merzbacher-like disorder (PMLD, a disorder of brain development and muscle function) [201][202][203][204][205][206][207]. The first report of SNAP29 involvement in CEDNIK noted that no N-and O-glycosylation defects were observed, although the authors did not describe how the patients were screened [206].…”

Section: Snaresmentioning

confidence: 99%

Sugary Logistics Gone Wrong: Membrane Trafficking and Congenital Disorders of Glycosylation

Linders

Peters

Beest

et al. 2020

IJMS

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Glycosylation is an important post-translational modification for both intracellular and secreted proteins. For glycosylation to occur, cargo must be transported after synthesis through the different compartments of the Golgi apparatus where distinct monosaccharides are sequentially bound and trimmed, resulting in increasingly complex branched glycan structures. Of utmost importance for this process is the intraorganellar environment of the Golgi. Each Golgi compartment has a distinct pH, which is maintained by the vacuolar H+-ATPase (V-ATPase). Moreover, tethering factors such as Golgins and the conserved oligomeric Golgi (COG) complex, in concert with coatomer (COPI) and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated membrane fusion, efficiently deliver glycosylation enzymes to the right Golgi compartment. Together, these factors maintain intra-Golgi trafficking of proteins involved in glycosylation and thereby enable proper glycosylation. However, pathogenic mutations in these factors can cause defective glycosylation and lead to diseases with a wide variety of symptoms such as liver dysfunction and skin and bone disorders. Collectively, this group of disorders is known as congenital disorders of glycosylation (CDG). Recent technological advances have enabled the robust identification of novel CDGs related to membrane trafficking components. In this review, we highlight differences and similarities between membrane trafficking-related CDGs.

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Section: Snaresmentioning

confidence: 99%

Sugary Logistics Gone Wrong: Membrane Trafficking and Congenital Disorders of Glycosylation

Linders

Peters

Beest

et al. 2020

IJMS

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“…Indeed, it was reported that loss of SNAP29 cause CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma), a rare recessive congenital syndrome. In CEDNIK patients, homozygous SNAP29 loss of function mutations cause a typical set of neurocutaneous traits that results in very poor life expectancy 4647484950. The alterations due to lack of SNAP29 have been analyzed in the stratum corneum of skin of patients, which presents an accumulation of glucosylceramides normally secreted towards the upper layers, suggesting the existence of a defect in secretion of lamellar granules containing lipids and proteolytic enzymes important for normal skin development.…”

Section: Snap29 and Diseasementioning

confidence: 99%

How to use a multipurpose SNARE: The emerging role of Snap29 in cellular health

Mastrodonato¹,

Morelli²,

Vaccari³

2018

CST

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Despite extensive study, regulation of membrane trafficking is incompletely understood. In particular, the specific role of SNARE (Soluble NSF Attachment REceptor) proteins for distinct trafficking steps and their mechanism of action, beyond the core function in membrane fusion, are still elusive. Snap29 is a SNARE protein related to Snap25 that gathered a lot of attention in recent years. Here, we review the study of Snap29 and its emerging involvement in autophagy, a self eating process that is key to cell adaptation to changing environments, and in other trafficking pathways. We also discuss Snap29 role in synaptic transmission and in cell division, which might extend the repertoire of SNARE-mediated functions. Finally, we present evidence connecting Snap29 to human disease, highlighting the importance of Snap29 function in tissue development and homeostasis.

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“…It has been reported by clinicians that CEDNIK patients display a severe central nervous system development deficiency and suffer from neurogenic and skeletal muscle hypotonia 31 . However, the pathogenesis of these symptoms has not been investigated.…”

Section: Resultsmentioning

confidence: 99%

“…In addition to be due to potentially impaired muscle functionality, reduced touch-evoked responses of snap29 K164* mutant larvae might echo nervous system manifestations of CEDNIK patients, which include psychomotor retardation 12 . In addition, absence of trigeminal motor neurons, which control mandibular arch muscles and mouth opening 33 in mutant fish, suggests a further cause for lack of swim bladder inflation and feeding impairment, the latter phenotype echoing the inability to feed of CEDNIK infants 31 .…”

Section: Discussionmentioning

confidence: 99%

A genetic model of CEDNIK syndrome in zebrafish highlights the role of the SNARE protein Snap29 in neuromotor and epidermal development

Mastrodonato

Beznoussenko

Mironov

et al. 2019

Sci Rep

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Homozygous mutations in SNAP29, encoding a SNARE protein mainly involved in membrane fusion, cause CEDNIK (Cerebral Dysgenesis, Neuropathy, Ichthyosis and Keratoderma), a rare congenital neurocutaneous syndrome associated with short life expectancy, whose pathogenesis is unclear. Here, we report the analysis of the first genetic model of CEDNIK in zebrafish. Strikingly, homozygous snap29 mutant larvae display CEDNIK-like features, such as microcephaly and skin defects. Consistent with Snap29 role in membrane fusion during autophagy, we observe accumulation of the autophagy markers p62 and LC3, and formation of aberrant multilamellar organelles and mitochondria. Importantly, we find high levels of apoptotic cell death during early development that might play a yet uncharacterized role in CEDNIK pathogenesis. Mutant larvae also display mouth opening problems, feeding impairment and swimming difficulties. These alterations correlate with defective trigeminal nerve formation and excess axonal branching. Since the paralog Snap25 is known to promote axonal branching, Snap29 might act in opposition with, or modulate Snap25 activity during neurodevelopment. Our vertebrate genetic model of CEDNIK extends the description in vivo of the multisystem defects due to loss of Snap29 and could provide the base to test compounds that might ameliorate traits of the disease.

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Cednik

Cited by 16 publications

References 13 publications

Sugary Logistics Gone Wrong: Membrane Trafficking and Congenital Disorders of Glycosylation

Sugary Logistics Gone Wrong: Membrane Trafficking and Congenital Disorders of Glycosylation

How to use a multipurpose SNARE: The emerging role of Snap29 in cellular health

A genetic model of CEDNIK syndrome in zebrafish highlights the role of the SNARE protein Snap29 in neuromotor and epidermal development

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