Human Molecular Genetics, 2001, Vol. 10, No. 5 497-505
© 2001 Oxford University Press
Co-regulation of survival of motor neuron (SMN) protein and its interactor SIP1 during development and in spinal muscular atrophy
1Klinische Forschergruppe Neuroregeneration, Department of Neurology, University of Würzburg, Josef-Schneider-Strasse 11, D-97080 Würzburg, Germany, 2Max-Planck Institute of Biochemistry, Am Klopferspitz 18a, D-82152 Martinsried, Germany, 3Institute of Human Genetics, University of Bonn, Wilhelmstrasse 31, D-53111 Bonn, Germany
Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by the degeneration of motor neurons in the spinal cord. The disease is caused by mutations of the survival of motor neuron 1 gene (SMN1), resulting in a reduced production of functional SMN protein. A major question unanswered thus far is why reduced amounts of ubiquitously expressed SMN protein specifically cause the degeneration of motor neurons without affecting other somatic cell types. In a first attempt to address this issue we have investigated the Smn interacting protein 1 (Sip1), with an emphasis on its developmental expression and subcellular distribution in spinal motor neurons in relation to Smn. By confocal immunofluorescence studies we provide evidence that a significant amount of Smn does not co-localize with Sip1 in neurites of motor neurons, indicating that Smn may exert motor neuron-specific functions that are not dependent on Sip1. Sip1 is highly expressed in the spinal cord during early development and expression decreases in parallel with Smn during postnatal development. Strikingly, reduced production of Smn as observed in cell lines derived from SMA patients or in a mouse model for SMA coincides with a simultaneous reduction of Sip1. The finding that expression of Sip1 and Smn is tightly co-regulated, together with the unique localization of Smn in neurites, may help in understanding the motor neuron-specific defects observed in SMA patients.
+ These authors contributed equally to this work.
§ To whom correspondence should be addressed. Tel: +49 89 8578 2475; Fax: +49 89 8578 3965; Email: ufischer@biochem.mpg.de
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