By studying families with sleep/wake disorders, Fu and Ptáček have shown that mutations that cause changes in the phosphorylation or acylation of the PER2 protein are responsible for regulating circadian rhythms.
Ptáček introduces the circadian clock and its relationship to sleep. He describes different sleep-wake behaviors including people who go to sleep and awaken exceptionally early or late. By studying families with an advanced sleep phase (ASP) phenotype, he and his colleagues showed that these individuals had a shortened circadian period. Further studies of families with similar sleep-wake behaviors have identified a number of mutations responsible for circadian rhythm regulation.
In Part 2 of the talk, Dr. Fu explains that studies of families with sleep disorders have shown that post-translational modifications of the PER2 protein are involved in regulating circadian rhythms. Casein kinase 1 phosphorylates PER2 and mutations in either CK1 or specific serine residues in PER2 result in an advanced sleep phase phenotype. O-GlcNAcylation of PER2 also participates in regulating circadian rhythms because O-GlcNAcylation blocks the sites usually phosphorylated by CK1.
Louis Ptáček leads the Division of Neurogenetics, in the Department of Neurology, at the University of California, San Francisco. He is also an Investigator of the Howard Hughes Medical Institute.Ptáček’s interest is in inherited disorders of the nervous system in human families and his early research identified mutations in several ion channels that caused episodic… Continue Reading
Ying-Hui Fu is a Professor of Neurology at the University of California, San Francisco where she collaborates with Dr. Ptáček in the Division of Neurogenetics. Research in her lab uses genetic tools to study neurodegenerative diseases, such as multiple sclerosis, and sleep/wake behaviors. Dr. Fu received her PhD from Ohio State University before moving to… Continue Reading