title: A zyxin-nectin interaction facilitates zyxin localization to cell-cell adhesions.
abstract: Cell-cell junction remodeling is associated with dramatic actin reorganizations. Several actin regulatory systems have been implicated in actin remodeling events as cell-cell contacts are assembled and disassembled, including zyxin/LPP-VASP complexes. These complexes facilitate strong cell-cell adhesion by maintaining actin-membrane connections. It has been proposed that zyxin and LPP localize to cell-cell junctions via a well-defined interaction with alpha-actinin. This was recently confirmed for LPP, but zyxin localization at cell-cell contacts occurs independently of alpha-actinin binding. Here we seek to map the zyxin sequence responsible for localization to cell-cell contacts and identify the protein that docks zyxin at this cellular location. Previous results have shown that a zyxin fragment excluding the alpha-actin binding site and the LIM domains (amino acids 51-392) can independently localize to cell-cell contacts. Here, expression of smaller zyxin fragments show that zyxin localization requires amino acids 230-280. A yeast-two-hybrid screen, using the central region of zyxin as bait, resulted in the identification of the cell-cell adhesion receptor nectin-4 as a zyxin binding partner. Further demonstrating zyxin-nectin interactions, zyxin binds the intracellular domain of nectin-2 in vitro. Depletion of nectin-2 from L cells expressing E-cadherin results in a loss of zyxin localization to cell-cell contacts, demonstrating that the zyxin-nectin interaction plays a critical role in zyxin targeting to these sites.
authors: Physiology and Developmental Biology, Brigham Young University, 574 WIDB, Provo, UT 84602, United States.
authors: S
authors: S
authors: Gregory Call
authors: Dan
authors: D
authors: Brereton
authors: Jace T
authors: JT
authors: Bullard
authors: Jarom Y
authors: JY
authors: Chung
authors: Kristen L
authors: KL
authors: Meacham
authors: David J
authors: DJ
authors: Morrell
authors: David J
authors: DJ
authors: Reeder
authors: Jeffrey T
authors: JT
authors: Schuler
authors: Austen D
authors: AD
authors: Slade
authors: Marc D H
authors: MD
authors: Hansen
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004285:Dogs; D006801:Humans; D000075983:Nectins; D017434:Protein Structure, Tertiary; D020798:Two-Hybrid System Techniques; D060589:Zyxin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D000075983:Nectins; C092842:ZYX protein, human; D060589:Zyxin