Neural (N-) cadherin is a transmembrane protein within adherens junctions that mediates cell-cell adhesion. It has 5 modular extracellular domains ( @entity42660 ) that bind 3 @entity460 ions between each of the modules. @entity460 binding is required for dimerization. @entity6076 is involved in diverse processes including tissue morphogenesis, excitatory synapse formation and dynamics, and @entity3 of @entity5 . During neurotransmission and tumorigenesis, fluctuations in extracellular pH occur, causing tissue @entity520 with associated physiological consequences. Studies reported here aim to determine the effect of pH on the dimerization properties of a truncated construct of @entity6076 containing @entity42660 -EC2. Since @entity6076 is an anionic protein, we hypothesized that acidification of solution would cause an increase in stability of the apo protein, a decrease in the @entity460 -binding affinity and a concomitant decrease in the formation of adhesive dimer. The stability of the apo monomer was increased, and the @entity460 -binding affinity was decreased at reduced pH, consistent with our hypothesis. Surprisingly, analytical SEC studies showed an increase in @entity460 -induced dimerization as solution pH decreased from 7.4 to 5.0. Salt-dependent dimerization studies indicated that electrostatic repulsion attenuates dimerization affinity. These results point to a possible electrostatic mechanism for moderating dimerization affinity of the Type I cadherin family. Extrapolating these results to cell adhesion in vivo leads to the assertion that decreased pH promotes adhesion by @entity6076 , thereby stabilizing synaptic junctions.

Impact of pH on the Structure and Function of XXXX .

@entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity520 :: ('MESH:D000138', 'Disease') :: ['acidosis'] @entity42660 :: ('4819', 'Gene') :: ['EC1-EC5', 'EC1'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastasis'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium', 'Calcium'] @entity6076 :: ('1000', 'Gene') :: ['N-cadherin']
@entity6076 :: (1000,Gene) :: ['Neural Cadherin']
