Mammalian Ceramide Synthases: Function and Perspectives

Dear Colleagues,

Ceramides, the central players in sphingolipid metabolism and important signaling molecules, have been implicated in the regulation of fundamental cellular processes such as proliferation, differentiation, motility, senescence and apoptosis. The key role in this regulation belongs to ceramide synthases (CerSes), enzymes responsible for ceramide biosynthesis, both de novo and from the salvage pathways. Mammalian ceramide synthases were discovered in 2002 through a homology search using the Lag1p motif of the yeast longevity associated gene. In the following years, more than 250 publications have been dedicated to ceramide synthases. Among these, the existence of six CerSes paralogs (both in humans and mice), the acyl-CoA specificities of each enzyme, CerSes membrane organization, differential expression of the CerSes in different tissues, their roles in in physiological processes and cell signaling, and the effects of individual CerS knockouts in mice have been established.

Nevertheless, our knowledge of these important players in cellular homeostasis is still fragmented. Each CerS has been annotated to have 2-3 transcripts, the role and tissue expression of which have not been established. The membrane topology of human ceramide synthases has not been experimentally determined, but rather deduced from predictions of hydrophobicity. However, different web tools provide slightly differing predictions of topological arrangement. Due to the fact that CerSes are integral membrane proteins, determination of their structures has not been performed. For the same reason, biochemical and biophysical characterization of CerS proteins is also challenging. While information on the regulation of ceramide synthases accumulates, the understanding of how enzyme levels and activities are controlled is lacking. Significant amounts of information have been accumulated on the biological effects of the enzymes knock-down, knock-out and inhibition, which has helped to outline the biological functions of CerSes. However, similar to the ceramides themselves, these functions are often context-specific, dependent on cell/tissue type, the presence of specific effectors, timing and other factors.

The purpose of the Special Issue “Mammalian Ceramide Synthases: function and perspectives” is to provide a current overview of the knowledge on ceramide synthases structure and function, their regulation, as well as their roles in health and disease. The goal is to highlight the recent advances in our understanding of the enzymes biology and their potential as pharmacological or nutritional targets for improvement of human health. Submissions of reviews, basic and translational research papers, as well as opinion papers are highly encouraged.

Dr. Natalia I. Krupenko
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• Sphingolipid metabolism
• ceramide signaling
• ceramide synthases
• CerS membrane organization
• CerS acyl chain specificity
• CerS regulation