Common and divergent roles for members of the mouse DCX superfamily.
The doublecortin-like (DCX) domains serve as protein-interaction platforms. DCX tandem domains appear in the product of the X-linked doublecortin (DCX) gene, in retinitis pigmentosa-1 (RP1), as well as in other gene products. Mutations in the human DCX gene are associated with abnormal neuronal migration, epilepsy, and mental retardation; mutations in RP1 are associated with a form of inherited blindness, while DCDC2 has been associated with dyslectic reading disabilities. Motivated by the possible importance of this gene family, a thorough analysis to detect all family members in the mouse was conducted. The DCX-repeat gene superfamily is composed of eleven paralogs, and we cloned the DCX domains from nine different genes. Our study questioned which functions attributed to the DCX domain, are conserved among the different members. Our results suggest that the proteins with the DCX-domain have conserved and unique roles in microtubule regulation and signal transduction. All the tested proteins stimulated microtubule assembly in vitro. Proteins with tandem repeats stabilized the microtubule cytoskeleton in transfected cells, while those with single repeats localized to actin-rich subcellular structures, or the nucleus. All tested proteins interacted with components of the JNK/MAP-kinase pathway, while only a subset interacted with Neurabin 2, and a nonoverlapping group demonstrated actin association. The sub-specialization of some members due to confined intracellular localization, and protein interactions may explain the success of this superfamily.
Coquelle
Frédéric M
FM
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Levy
Talia
T
Bergmann
Sven
S
Wolf
Sharon Grayer
SG
Bar-El
Daniela
D
Sapir
Tamar
T
Brody
Yehuda
Y
Orr
Irit
I
Barkai
Naama
N
Eichele
Gregor
G
Reiner
Orly
O
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D017124:Conserved Sequence; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D008938:Mitosis / Q000502:physiology; D005810:Multigene Family / Q000502:physiology*; D009479:Neuropeptides / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology
C000714328:DCX protein, human; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides