Characterisation of PGs1, a subunit of a protein complex co-purfying with tubulin polyglutamylase

Centre de Recherches de Biochimie Macromoléculaire, CNRS, 34293 Montpellier, France.
Journal of Cell Science (Impact Factor: 5.43). 11/2003; 116(Pt 20):4181-90. DOI: 10.1242/jcs.00743
Source: PubMed


Polyglutamylation is a post-translational modification initially discovered on tubulin. It has been implicated in multiple microtubule functions, including neuronal differentiation, axonemal beating and stability of the centrioles, and shown to modulate the interaction between tubulin and microtubule associated proteins. The enzymes catalysing this modification are not yet known. Starting with a partially purified fraction of mouse brain tubulin polyglutamylase, monoclonal antibodies were raised and used to further purify the enzyme by immunoprecipitation. The purified enzyme complex (Mr 360x103) displayed at least three major polypeptides of 32, 50 and 80x103, present in stochiometric amounts. We show that the 32x103 subunit is encoded by the mouse gene GTRGEO22, the mutation of which has recently been implicated in multiple defects in mice, including male sterility. We demonstrate that this subunit, called PGs1, has no catalytic activity on its own, but is implicated in the localisation of the enzyme at major sites of polyglutamylation, i.e. neurones, axonemes and centrioles.

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    • "are inactive in the experiment , despite the presence of core and extended TTL domains ( Janke et al . 2005 ; Ikegami et al . 2006 ; van Dijk et al . 2007 ) , raising the possibility that co - factors might be needed for full PG activity . Indeed , TTLL1 ( PGs3 ) was isolated from brain as part of components with PG activity , including PGs1 – 5 ( Regnard et al . 2003 ; Janke et al . 2005 ) . Further analyses revealed that TTLL4 , 5 , and 7 preferentially initiate glutamylation , whereas TTLL6 , 11 , and 13 preferentially elongate the side chain . All TTLL members ( TTLL1 – 13 ) are expressed in the developing hippocampus , and some TTLL members with PG activity ( i . e . , TTLL6 and 11 ) seem to be "
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