Conflict of interest

physical connections like cytoskeleton-associated protein 4 (CKAP4) which is a transmembrane protein that further to its function as receptor also links endoplasmic reticulum (ER) to the cytoskeleton [57]. It is predictable that a membrane compact microdomain be involved in such function, in order to provide further support to the anchor. Such hypothesis is sustained by the fact that CKAP4 is a reversibly palmitoylated protein [58], and it is well described that palmitoylation of cytoplasmic proteins regulates the interaction of these soluble proteins with specific membranes or membrane domains. It is possible that palmitoylation controls the conformation of transmembrane segments, to modify the affinity of a membrane protein for specific

Finally one should consider that both lipids and proteins for microdomains constructs are synthesized in the ER/Golgi before transport to the plasma membrane and, indeed, those proteins can be in a detergent-resistant, cholesterol-dependent state while residing there or in

Our purpose was to contribute to the biological characterization of this Dhcr7T93M/T93M hypomorphic mouse model and identify differences that could help to go deeper in the

Proteomic analysis of DRMs of skeletal muscular samples clearly show differences between SLOS and wild-type mice, concerning proteins linked to membranes. The employed methodology allowed us to identify further alterations related with calcium homeostasis and membrane trafficking associated with SLOS and detected, for the first time, changes in mitochondrial

To the best of our knowledge, this is the first research study focusing on the skeletal muscle of SLOS. The differential protein expression profile identified will open the way to comparative studies with more severally affected disease mice models as well as to similar approaches in

The authors are thankful to Prof Forbes D. Porter and Doctor Christopher A. Wassif from NIH who kindly provided the genetically modified mice model of SLOS used in this investigation. FDP and CAW are supported by the intramural research program of 30 the Eunice Kennedy

Requimte received finnantial support from the European Union (FEDER funds POCI/01/0145/ FEDER/007265) and National Funds (FCT/MEC, Fundação para a Ciência e Tecnologia and Ministério da Educação e Ciência) under the Partnership Agreement PT2020 UID/QUI/50006/2013.

human cells which may be helpful to uncover cellular mechanisms related to SLOS.

Shriver National Institute of Child Health and Human Development.

membrane domains and to control protein–protein interactions [59].

vesicle trafficking [60].

136 Cholesterol - Good, Bad and the Heart

understanding of SLOS physiopathology.

energy metabolism in this mouse model.

Acknowledgements

4. Conclusion

The authors declare that there are no conflicts of interest.
