The Role of Atypical PKC in the Plasticity of the Circadian Clock in the Rat Suprachiasmatic Nucleus

In mammals, the daily rhythms of biological functions are generated by the master circadian clock, which locates within the suprachiasmatic nucleus (SCN) of the hypothalamus. The endogenous circadian rhythms generated by the SCN are actively synchronized by the environmental light. The photic signals are transferred by the excitatory neurotransmitter, glutamate (GLU), via the retinohypothalamic tract from the retina to the SCN. Light/GLU pulses can reset the mammalian circadian clock at specific times: in the early night, light/GLU delays clock phase, whereas in the late night, light/GLU advances it. The changes of clock temporal status by light/GLU are highly regulated by phosphorylation events. In this study, we examined the role of atypical protein kinase C (aPKC) in GLU signaling. We found that the phosphotransferase activity of aPKC is increased significantly by GLU treatment to SCN brain slices at CT 14 in the early night. Disruption of aPKC phosphotransferase activity completely blocks GLU-induced phase delays in the early night, but not phase advances in the late night, demonstrating that aPKC is essential for GLU-induced phase delays only. Furthermore, we found that aPKC is activated by GLU by inducing the protein level of aPKC. Studies on glycogen synthase kinase-3beta (GSK-3beta) and TIMELESS show that these two proteins may be regulated by aPKC in the rat SCN. A model is proposed that describes the current understanding of the glutamate signaling pathway mediated by aPKC in the early night in the rat SCN.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Cell and Developmental Biology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Huang, Sufang

Contributors dc:contributor

• David Clayton
• Gillette, Martha U.

• Biology, Neuroscience

Language dc:language

eng

Identifier

(MiAaPQ)AAI3337797

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/86316