PMID- 16877344
OWN - NLM
STAT- MEDLINE
DCOM- 20060901
LR  - 20201113
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 169
IP  - 2
DP  - 2006 Aug
TI  - A novel N14Y mutation in Connexin26 in keratitis-ichthyosis-deafness syndrome: 
      analyses of altered gap junctional communication and molecular structure of N 
      terminus of mutated Connexin26.
PG  - 416-23
AB  - Connexins (Cxs) are transmembranous proteins that connect adjacent cells via 
      channels known as gap junctions. The N-terminal 21 amino acids of Cx26 are 
      located at the cytoplasmic side of the channel pore and are thought to be 
      essential for the regulation of channel selectivity. We have found a novel 
      mutation, N14Y, in the N-terminal domain of Cx26 in a case of 
      keratitis-ichthyosis-deafness syndrome. Reduced gap junctional intercellular 
      communication was observed in the patient's keratinocytes by the dye transfer 
      assay using scrape-loading methods. The effect of this mutation on molecular 
      structure was investigated using synthetic N-terminal peptides from both 
      wild-type and mutated Cx26. Two-dimensional (1)H nuclear magnetic resonance and 
      circular dichroism measurements demonstrated that the secondary structures of 
      these two model peptides are similar to each other. However, several novel 
      nuclear Overhauser effect signals appeared in the N14Y mutant, and the secondary 
      structure of the mutant peptide was more susceptible to induction of 
      2,2,2-trifluoroethanol than wild type. Thus, it is likely that the N14Y mutation 
      induces a change in local structural flexibility of the N-terminal domain, which 
      is important for exerting the activity of the channel function, resulting in 
      impaired gap junctional intercellular communication.
FAU - Arita, Ken
AU  - Arita K
AD  - Department of Dermatology, Hokkaido University Graduate School of Medicine, North 
      15 West 7, Kita-ku, Sapporo 060-8638, Japan. ariken@med.hokudai.ac.jp
FAU - Akiyama, Masashi
AU  - Akiyama M
FAU - Aizawa, Tomoyasu
AU  - Aizawa T
FAU - Umetsu, Yoshitaka
AU  - Umetsu Y
FAU - Segawa, Ikuo
AU  - Segawa I
FAU - Goto, Maki
AU  - Goto M
FAU - Sawamura, Daisuke
AU  - Sawamura D
FAU - Demura, Makoto
AU  - Demura M
FAU - Kawano, Keiichi
AU  - Kawano K
FAU - Shimizu, Hiroshi
AU  - Shimizu H
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Amino Acids)
RN  - 0 (Connexins)
RN  - 0 (GJB2 protein, human)
RN  - 0 (Mutant Proteins)
RN  - 127120-53-0 (Connexin 26)
SB  - IM
MH  - 3T3 Cells
MH  - Amino Acids/chemistry
MH  - Animals
MH  - Base Sequence
MH  - Cells, Cultured
MH  - Child, Preschool
MH  - Circular Dichroism
MH  - Connexin 26
MH  - Connexins/chemistry/*genetics
MH  - DNA Mutational Analysis
MH  - Deafness/*genetics
MH  - Female
MH  - Gap Junctions/*pathology/ultrastructure
MH  - Humans
MH  - Ichthyosis/*genetics
MH  - Keratinocytes/cytology/pathology
MH  - Keratitis/*genetics
MH  - Mice
MH  - Molecular Sequence Data
MH  - Mutant Proteins/*chemistry/genetics
MH  - Mutation/*genetics
MH  - Nuclear Magnetic Resonance, Biomolecular
MH  - Skin/cytology/pathology/ultrastructure
MH  - Syndrome
PMC - PMC1698798
EDAT- 2006/08/01 09:00
MHDA- 2006/09/02 09:00
PMCR- 2007/08/01
CRDT- 2006/08/01 09:00
PHST- 2006/08/01 09:00 [pubmed]
PHST- 2006/09/02 09:00 [medline]
PHST- 2006/08/01 09:00 [entrez]
PHST- 2007/08/01 00:00 [pmc-release]
AID - S0002-9440(10)62725-3 [pii]
AID - 10.2353/ajpath.2006.051242 [doi]
PST - ppublish
SO  - Am J Pathol. 2006 Aug;169(2):416-23. doi: 10.2353/ajpath.2006.051242.