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Molecular and Cellular Biology, February 2006, p. 1510-1517, Vol. 26, No. 4
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.4.1510-1517.2006

Mouse Disabled 1 Regulates the Nuclear Position of Neurons in a Drosophila Eye Model

Albéna Pramatarova,^1, Pawel G. Ochalski,^1, Chi-Hon Lee,² and Brian W. Howell^1*

Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, 35 Convent Dr., Bethesda, Maryland 20892,¹ Unit of Neuronal Connectivity, Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892²

Received 5 October 2005/ Accepted 9 November 2005

Nucleokinesis has recently been suggested as a critical regulator of neuronal migration. Here we show that Disabled 1 (Dab1), which is required for neuronal positioning in mammals, regulates the nuclear position of postmitotic neurons in a phosphorylation-site dependent manner. Dab1 expression in the Drosophila visual system partially rescues nuclear position defects caused by a mutation in the Dynactin subunit Glued. Furthermore, we observed that a loss-of-function allele of amyloid precursor protein (APP)-like, a kinesin cargo receptor, enhanced the severity of a Dab1 overexpression phenotype characterized by misplaced nuclei in the adult retina. In mammalian neurons, overexpression of APP reduced the ability of Reelin to induce Dab1 tyrosine phosphorylation, suggesting an antagonistic relationship between APP family members and Dab1 function. This is the first evidence that signaling which regulates Dab1 tyrosine phosphorylation determines nuclear positioning through Dab1-mediated influences on microtubule motor proteins in a subset of neurons.

These individuals contributed equally to this paper.

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