Chibby promotes ciliary vesicle formation and basal body docking during airway cell differentiation

J Cell Biol. 2014 Oct 13;207(1):123-37. doi: 10.1083/jcb.201406140.

Abstract

Airway multiciliated epithelial cells play crucial roles in the mucosal defense system, but their differentiation process remains poorly understood. Mice lacking the basal body component Chibby (Cby) exhibit impaired mucociliary transport caused by defective ciliogenesis, resulting in chronic airway infection. In this paper, using primary cultures of mouse tracheal epithelial cells, we show that Cby facilitates basal body docking to the apical cell membrane through proper formation of ciliary vesicles at the distal appendage during the early stages of ciliogenesis. Cby is recruited to the distal appendages of centrioles via physical interaction with the distal appendage protein CEP164. Cby then associates with the membrane trafficking machinery component Rabin8, a guanine nucleotide exchange factor for the small guanosine triphosphatase Rab8, to promote recruitment of Rab8 and efficient assembly of ciliary vesicles. Thus, our study identifies Cby as a key regulator of ciliary vesicle formation and basal body docking during the differentiation of airway ciliated cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Motifs / genetics
  • Animals
  • Basal Bodies / physiology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Centrioles / physiology
  • Cilia / genetics
  • Cilia / metabolism*
  • Epithelial Cells / cytology*
  • Germinal Center Kinases
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microtubule Proteins / genetics
  • Microtubule Proteins / metabolism*
  • Mucociliary Clearance / genetics
  • Naphthalenes
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Structure, Tertiary
  • Protein Transport
  • RNA Interference
  • RNA, Small Interfering
  • Respiratory Mucosa / cytology*
  • rab GTP-Binding Proteins / metabolism

Substances

  • CEP164 protein, human
  • Carrier Proteins
  • Chibby protein, mouse
  • Germinal Center Kinases
  • Microtubule Proteins
  • Naphthalenes
  • Nuclear Proteins
  • RNA, Small Interfering
  • Rab8 protein, mouse
  • naphthalene
  • Protein Serine-Threonine Kinases
  • rab GTP-Binding Proteins