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RESEARCH PAPER

The microtubule plus-end-tracking protein CLIP-170 associates with the spermatid manchette and is essential for spermatogenesis

¹ Department of Cell Biology and Genetics, ² Department of Reproduction and Development, and ³ Department of Neuroscience, Erasmus MC, 3000 DR Rotterdam, The Netherlands; ⁴ Center for Electron Microscopy, Department of Molecular Cell Biology, Leiden University Medical Center, 2300 RA Leiden, The Netherlands; ⁵ Department of Medical Oncology, University Medical Center, 3584 CG Utrecht, The Netherlands

CLIP-170 is a microtubule "plus-end-tracking protein" implicated in the control of microtubule dynamics, dynactin localization, and the linking of endosomes to microtubules. To investigate the function of mouse CLIP-170, we generated CLIP-170 knockout and GFP-CLIP-170 knock-in alleles. Residual CLIP-170 is detected in lungs and embryos of homozygous CLIP-170 knockout mice, but not in other tissues and cell types, indicating that we have generated a hypomorphic mutant. Homozygous CLIP-170 knockout mice are viable and appear normal. However, male knockout mice are subfertile and produce sperm with abnormal heads. Using the knock-in mice, we followed GFP-CLIP-170 expression and behavior in dissected, live testis tubules. We detect plus-end-tracking GFP-CLIP-170 in spermatogonia. As spermatogenesis proceeds, GFP-CLIP-170 expression increases and the fusion protein strongly marks syncytia of differentiated spermatogonia and early prophase spermatocytes. Subsequently GFP-CLIP-170 levels drop, but during spermiogenesis (post-meiotic development), GFP-CLIP-170 accumulates again and is present on spermatid manchettes and centrosomes. Bleaching studies show that, as spermatogenesis progresses, GFP-CLIP-170 converts from a mobile plus-end-tracking protein to a relatively immobile protein. We propose that CLIP-170 has a structural function in the male germline, in particular in spermatid differentiation and sperm head shaping.

[Keywords: Microtubules; plus-end-tracking proteins; CLIP-170; spermatogenesis; spermatid manchette]

Received March 20, 2005; revised version accepted July 13, 2005.

⁶ Present address: INSERM U583, Institut des Neurosciences de Montpellier, Hôpital Saint-Eloi, 80 avenue Augustin Fliche, BP 74103, 34091 Montpellier Cedex 5, France.

⁷ Corresponding author.

E-MAIL n.galjart{at}erasmusmc.nl; FAX 31-10-4089468.

Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.344505.

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