LIP1, a cytoplasmic protein functionally linked to the Peutz-Jeghers syndrome kinase LKB1.

LIP1, a cytoplasmic protein functionally linked to the Peutz-Jeghers syndrome kinase LKB1. LKB1 is a serine/threonine kinase which is inactivated by mutation in the Peutz-Jeghers polyposis and cancer predisposition syndrome (PJS). We have identified a novel leucine-rich repeat containing protein, LIP1, that interacts with LKB1. The LIP1 gene consists of 25 exons, maps to human chromosome 2q36 and encodes a protein of 121 kDa. LIP1 appears to be a cytoplasmically located protein whereas we and others have shown previously that LKB1 is predominantly nuclear, with only a small proportion of cells showing strong cytoplasmic expression. However, when LKB1 and LIP1 are co-expressed, the proportion of cytoplasmic LKB1 dramatically increases, suggesting that LIP1 may regulate LKB1 function by controlling its subcellular localization. Ectopic expression of both LKB1 and LIP1 in Xenopus embryos induces a secondary body axis, providing further evidence for a functional link between the two proteins. This phenotype resembles the effects of ectopic expression of TGF beta superfamily members and their downstream effectors. A possible role for LIP1 and LKB1 in TGF beta signalling is supported by the observation that LIP1 interacts with the TGF beta -regulated transcription factor SMAD4, forming a LKB1-LIP1-SMAD4 ternary complex. SMAD4 mutations give rise to juvenile polyposis syndrome, which is clinically similar to PJS. Our data suggest an unsuspected mechanistic link between these two syndromes

Initial motor axon outgrowth from the developing central nervous system

Rat and chick studies show that the earliest motor rootlet axon bundles emerge from all levels of the neural tube between radial glial end feet which comprise the presumptive glia limitans. The loose arrangement of the end feet at the time of emergence facilitates this passage. The points of emergence are regularly spaced in relation to the long axis of the neural tube and are not defined by any cell contact with its surface. Each rootlet carries a covering of basal lamina from the neural tube surface, which forms a sleeve around it. It is only after bundles of ventral rootlet axons have emerged that cells associate with them, forming clusters on the rootlet surface at a distance peripheral to the CNS surface of both species. A tight collar of glial end feet develops around the axon bundle at the neural tube surface shortly after initial emergence. These arrangements are in sharp contrast to those seen in the sensory rootlets, where clusters of boundary cap cells prefigure the sensory entry zones at the attachments of the prospective dorsal spinal and cranial sensory rootlets. Boundary cap cells resemble cluster cells and a neural crest origin seems the most likely for them. The study clearly demonstrates that no features resembling boundary caps are found in relation to the developing motor exit points