Regulation of apoptosis and neurite extension by FKBP38 is required for neural tube formation in the mouse

Michiko Shirane, Masaharu Ogawa, Jun Motoyama, Keiichi Nakayama

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

FKBP38 (also known as FKBP8) is a transmembrane chaperone protein that inhibits apoptosis by recruiting the anti-apoptotic proteins Bcl-2 and Bcl-x L to mitochondria. We have now generated mice harboring a loss-of-function mutation in Fkbp38. The Fkbp38-/- mice die soon after birth manifesting defects in neural tube closure in the thoraco-lumbar-sacral region (spina bifida) as well as skeletal defects including scoliosis, rib deformities, club foot and curled tail. The neuroepithelium is disorganized and that formation of dorsal root ganglia is defective in Fkbp38-/- embryos, likely as a result of an increased frequency of apoptosis and aberrant migration of neuronal cells. Furthermore, the extension of nerve fibers in the spinal cord is abnormal in the mutant embryos. To explore the mechanisms underlying these characteristics, we screened for proteins that interact with FKBP38 in the yeast two-hybrid system and thereby identified protrudin, a protein that promotes process formation by regulating membrane trafficking. Protrudin was found to be hyperphosphorylated in the brain of Fkbp38-/- mice, suggesting that FKBP38 regulates protrudin-dependent membrane recycling and neurite outgrowth. Together, our findings suggest that FKBP38 is required for neuroectodermal organization during neural tube formation as a result of its anti-apoptotic activity and regulation of neurite extension.

Original languageEnglish
Pages (from-to)635-651
Number of pages17
JournalGenes to Cells
Volume13
Issue number6
DOIs
Publication statusPublished - Jun 1 2008

Fingerprint

Neural Tube
Neurites
Apoptosis
Embryonic Structures
Sacrococcygeal Region
Foot Deformities
Lumbosacral Region
Two-Hybrid System Techniques
Apoptosis Regulatory Proteins
Proteins
Spinal Dysraphism
Membranes
Spinal Ganglia
Scoliosis
Ribs
Nerve Fibers
Cell Movement
Tail
Spinal Cord
Mitochondria

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

Cite this

Regulation of apoptosis and neurite extension by FKBP38 is required for neural tube formation in the mouse. / Shirane, Michiko; Ogawa, Masaharu; Motoyama, Jun; Nakayama, Keiichi.

In: Genes to Cells, Vol. 13, No. 6, 01.06.2008, p. 635-651.

Research output: Contribution to journalArticle

Shirane, Michiko ; Ogawa, Masaharu ; Motoyama, Jun ; Nakayama, Keiichi. / Regulation of apoptosis and neurite extension by FKBP38 is required for neural tube formation in the mouse. In: Genes to Cells. 2008 ; Vol. 13, No. 6. pp. 635-651.
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