The microtubule-associated protein DCAMKL1 regulates osteoblast function via repression of Runx2. Academic Article uri icon

Overview

abstract

  • Osteoblasts are responsible for the formation and mineralization of the skeleton. To identify novel regulators of osteoblast differentiation, we conducted an unbiased forward genetic screen using a lentiviral-based shRNA library. This functional genomics analysis led to the identification of the microtubule-associated protein DCAMKL1 (Doublecortin-like and CAM kinase-like 1) as a novel regulator of osteogenesis. Mice with a targeted disruption of Dcamkl1 displayed elevated bone mass secondary to increased bone formation by osteoblasts. Molecular experiments demonstrated that DCAMKL1 represses osteoblast activation by antagonizing Runx2, the master transcription factor in osteoblasts. Key elements of the cleidocranial dysplasia phenotype observed in Runx2(+/-) mice are reversed by the introduction of a Dcamkl1-null allele. Our results establish a genetic linkage between these two proteins in vivo and demonstrate that DCAMKL1 is a physiologically relevant regulator of anabolic bone formation.

publication date

  • August 5, 2013

Research

keywords

  • Core Binding Factor Alpha 1 Subunit
  • Intracellular Signaling Peptides and Proteins
  • Microtubules
  • Osteoblasts
  • Protein Serine-Threonine Kinases
  • Protein-Serine-Threonine Kinases

Identity

PubMed Central ID

  • PMC3754873

Scopus Document Identifier

  • 84884252345

Digital Object Identifier (DOI)

  • 10.1084/jem.20111790

PubMed ID

  • 23918955

Additional Document Info

volume

  • 210

issue

  • 9