Stories of spinster with various faces: from courtship rejection to tumor metastasis rejection

Abstract

The Drosophila spinster (spin) mutant was isolated as a mutant that showed abnormal morphology and function in the nervous system. The spin defect induces neural degeneration similar to human lysosomal storage diseases. Various studies have shown that Spin proteins are localized in lysosomes and participate in the late stages of the autophagic process. Vertebrates have three spinster orthologs, Spns1, Spns2, and Spns3. A defect in Spns1 caused a short lifespan with aberrant lysosomal function in zebrafish. Spns2 was originally isolated as the gene responsible for abnormal heart development and was identified as a sphingosine 1-phosphate transporter in zebrafish. An endothelial cell-specific defect in Spns2 resulted in impaired egress of lymphocytes and the prevention of tumor metastasis in mice. Herein, I reviewed the history of spin/Spns research and discussed the conserved and newly diverged spin/Spns function and possible implications for human diseases.

Keywords:

• Spinster
• lysosome
• autophagy
• sphingosine 1-phosphate

Acknowledgments

I dedicate this paper to Dr. Daisuke Yamamoto, father of spinster, for his great contribution to the field of behavioral genetics. I thank Drs. Ohmuraya and Sugahara from Hyogo College of Medicine for their valuable comments, and Dr. Tanimoto from Tohoku University for the opportunity to participate in this special issue. I also thank Edanz Group (www.edanzediting.com) for editing a draft of this manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by an internal grant from Hyogo College of Medicine.