Toward an understanding of cochlear homeostasis: the impact of location and the role of OCP1 and OCP2.
The central role of the supporting cell population, or epithelial support complex (ESC), in cochlear homeostasis has gained general acceptance. That the details of this role may vary markedly with location, however, remains poorly appreciated. For example, the K+ recirculation pathway may well be dictated by position along the cochlear axis: a perilymphatic route near the apex and a transcellular one near the base. The ESC expresses very high levels of OCP1 and OCP2, now known to be components of a novel, organ of Corti (OC)-specific SCF ubiquitin ligase (SCF(OCP1)). In the SCF(OCP1) cnmplex, OCP1 presumably binds selected protein targets, positioning them for ubiquitination. The recent demonstration that recombinant OCP1 interacts non-covalently with Cx26 suggests that the connexins may be target proteins for SCF(OCP1). Although ubiquitination has classically been viewed as a signal for subsequent destruction by the 26S proteasome, the energy-limited state of the OC prompts consideration of alternative fates, e.g. reversible internalization. The ESC also expresses several components of the Wingless/Wnt signaling pathway. Significantly, two of the gap-junction proteins expressed in the OC, Cx43 and Cx30, are known targets of the Wnt pathway. On the basis of these observations, a working hypothesis is proposed wherein the Wnt pathway activates connexin expression, while OCP1 regulates its degradation.
Thalmann
Ruediger
R
Department of Otolaryngology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. thalmannr@msnotes.wustl.edu
Henzl
Michael T
MT
Killick
Richard
R
Ignatova
Elena G
EG
Thalmann
Isolde
I
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003051:Cochlea / Q000033:anatomy & histology* / Q000502:physiology*; D000072259:Connexin 26; D017630:Connexins; D044783:F-Box Proteins; D017629:Gap Junctions / Q000378:metabolism; D006168:Guinea Pigs; D006706:Homeostasis; D009419:Nerve Tissue Proteins; D009925:Organ of Corti / Q000502:physiology*; D010453:Peptide Synthases / Q000378:metabolism*; D044843:SKP Cullin F-Box Protein Ligases; D012680:Sensitivity and Specificity; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D018797:Cell Cycle Proteins; D017630:Connexins; D044783:F-Box Proteins; C485508:FBXO2 protein, human; C000607042:GJB2 protein, human; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000072259:Connexin 26; D044843:SKP Cullin F-Box Protein Ligases; D010453:Peptide Synthases