Goodpasture Antigen-binding Protein (GPBP) Directs Myofibril Formation: IDENTIFICATION OF INTRACELLULAR DOWNSTREAM EFFECTOR 130-kDa GPBP-INTERACTING PROTEIN (GIP130)

Francisco Revert-Ros,Ernesto López-Pascual,Froilán Granero-Moltó,Jesús Macías,Richard Breyer,Roy Zent,Billy G Hudson,Anas Saadeddin,Fernando Revert,Raül Blasco,Carmen Navarro,Deborah Burks,Juan Saus

doi:10.1074/jbc.m111.249458

Abstract

Goodpasture antigen-binding protein-1 (GPBP-1) is an exportable non-conventional Ser/Thr kinase that regulates glomerular basement membrane collagen organization. Here we provide evidence that GPBP-1 accumulates in the cytoplasm of differentiating mouse myoblasts prior to myosin synthesis. Myoblasts deficient in GPBP-1 display defective myofibril formation, whereas myofibrils assemble with enhanced efficiency in those overexpressing GPBP-1. We also show that GPBP-1 targets the previously unidentified GIP130 (GPBP-interacting protein of 130 kDa), which binds to myosin and promotes its myofibrillar assembly. This report reveals that GPBP-1 directs myofibril formation, an observation that expands its reported role in supramolecular organization of structural proteins to the intracellular compartment.

Highlights

Goodpasture antigen-binding protein-1 (GPBP-1) is a non-conventional kinase that regulates glomerular basement membrane collagen organization
We reveal that the targeting of GIP130 by GPBP-1 is critical for myofibrillar organization in skeletal muscle
Our data show that accumulation of GPBP-1 in the cytoplasm is accomplished by down-regulating alternative mRNA expression (GPBP-2 and -3)

Summary

Background

GPBP-1 is a non-conventional kinase that regulates glomerular basement membrane collagen organization. Goodpasture antigen-binding protein-1 (GPBP-1) is an exportable non-conventional Ser/Thr kinase that regulates glomerular basement membrane collagen organization. This report reveals that GPBP-1 directs myofibril formation, an observation that expands its reported role in supramolecular organization of structural proteins to the intracellular compartment. Our results reveal that Col4a3bp is critical for myogenesis and that GPBP-1 mediates myofibril myosin assembly through the targeting of the previously unrecognized GIP130 (GPBP-interacting protein of 130 kDa). Our data reveal that GPBP-1 regulates supramolecular organization of structural proteins at both extracellular (i.e. type IV collagen) and intracellular (i.e. myosin) compartments

EXPERIMENTAL PROCEDURES

RESULTS

DISCUSSION