Specific sphingolipid content decrease in Cerkl knockdown mouse retinas

Alejandro Garanto, Nawajes Mandal, Meritxell Egido-Gabás, Gemma Marfany, Gemma Fabriàs, Robert E. Anderson, Josefina Casas, Roser Gonzàlez-Duarte

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Sphingolipids (SPLs) are finely tuned structural compounds and bioactive molecules involved in membrane fluidity and cellular homeostasis. The core sphingolipid, ceramide (CER), and its derivatives, regulate several crucial processes in neuronal cells, among them cell differentiation, cell-cell interactions, membrane conductance, synaptic transmission, and apoptosis. Mutations in Ceramide Kinase-Like (CERKL) cause autosomal recessive Retinitis Pigmentosa and Cone Rod Dystrophy. The presence of a conserved lipid kinase domain and the overall similarity with CERK suggested that CERKL might play a role in the SPL metabolism as a CER kinase. Unfortunately, CERKL function and substrate(s), as well as its contribution to the retinal etiopathology, remain as yet unknown. In this work we aimed to characterize the mouse retinal sphingolipidome by UPLC-TOF to first, thoroughly investigate the SPL composition of the murine retina, compare it to our Cerkl-/- model, and finally assess new possible CERKL substrates by phosphorus quantification and protein-lipid overlay. Our results showed a consistent and notable decrease of the retinal SPL content (mainly ranging from 30% to 60%) in the Cerkl-/- compared to WT retinas, which was particularly evident in the glucosyl/galactosyl ceramide species (Glc/GalCer) whereas the phospholipids and neutral lipids remained unaltered. Moreover, evidence in favor of CERKL binding to GlcCer, GalCer and sphingomyelin has been gathered. Altogether, these results highlight the involvement of CERKL in the SPL metabolism, question its role as a kinase, and open new scenarios concerning its function.

Original languageEnglish (US)
Pages (from-to)96-106
Number of pages11
JournalExperimental Eye Research
Volume110
DOIs
StatePublished - May 1 2013

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Sphingolipids
Retina
Lipids
Phosphotransferases
Galactosylceramides
Glucosylceramides
Membrane Fluidity
Retinitis Pigmentosa
Sphingomyelins
Ceramides
ceramide kinase
Cell Communication
Synaptic Transmission
Phosphorus
Cell Differentiation
Phospholipids
Homeostasis
Cell Membrane
Apoptosis
Mutation

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Garanto, A., Mandal, N., Egido-Gabás, M., Marfany, G., Fabriàs, G., Anderson, R. E., ... Gonzàlez-Duarte, R. (2013). Specific sphingolipid content decrease in Cerkl knockdown mouse retinas. Experimental Eye Research, 110, 96-106. https://doi.org/10.1016/j.exer.2013.03.003

Specific sphingolipid content decrease in Cerkl knockdown mouse retinas. / Garanto, Alejandro; Mandal, Nawajes; Egido-Gabás, Meritxell; Marfany, Gemma; Fabriàs, Gemma; Anderson, Robert E.; Casas, Josefina; Gonzàlez-Duarte, Roser.

In: Experimental Eye Research, Vol. 110, 01.05.2013, p. 96-106.

Research output: Contribution to journalArticle

Garanto, A, Mandal, N, Egido-Gabás, M, Marfany, G, Fabriàs, G, Anderson, RE, Casas, J & Gonzàlez-Duarte, R 2013, 'Specific sphingolipid content decrease in Cerkl knockdown mouse retinas', Experimental Eye Research, vol. 110, pp. 96-106. https://doi.org/10.1016/j.exer.2013.03.003
Garanto, Alejandro ; Mandal, Nawajes ; Egido-Gabás, Meritxell ; Marfany, Gemma ; Fabriàs, Gemma ; Anderson, Robert E. ; Casas, Josefina ; Gonzàlez-Duarte, Roser. / Specific sphingolipid content decrease in Cerkl knockdown mouse retinas. In: Experimental Eye Research. 2013 ; Vol. 110. pp. 96-106.
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