Hypotheses concerning how Otx2 makes its incredible journey: a hitchhiker on the road to Rome?

From work carried out largely by Alain Prochiantz and his co-workers at the College de France (Sugiyama et al., 2008; Beurdeley et al., 2012; Carlier et al., 2013; Smythies and Edelstein, 2013; Spatazza et al., 2013a,b), it is now known that the homeoprotein and transcription factor molecule Otx2 possesses a very unusual property. This flexible molecule is able to cross cell membranes without using a specific energy-requiring carrier. The entry mechanism involves organizing a micelle structure out of the planar lipoprotein plasma membrane via interactions between charged residues and lipophilic interactions. This micelle carries the molecule of Otx2 across the membrane. It has been shown that the membrane exit mechanism of a related molecule, Engrailed 2, is different and involves the formation of energy-dependent calveoli-like vesicles (Sugiyama et al., 2008; Carlier et al., 2013; Spatazza et al., 2013a). These vesicles are delivered into the interior of the cell. When injected into the eye Otx2 is transported to the visual cortex where it enters PV-expressing GABAergic INs (PVs), which it activates (Sugiyama et al., 2008; Beurdeley et al., 2012; Carlier et al., 2013; Spatazza et al., 2013a,b). During natural development, following the opening of the eyes, Otx2 molecules accumulate “gradually” in the visual cortex. In vivo, the molecule at source is synthesized in a retinal bipolar cell and transmitted to a retinal ganglion cell. The ganglion cell contains no Otx2 mRNA. At the other end of the journey, neither does the cortical cell; its Otx2 is transmitted from neurons in the lateral geniculate nucleus (LGN).

• Publication year

  2013

• Venue

  Frontiers in Molecular Neuroscience

• Publication date

  2013-12-30

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3389/fnmol.2013.00055PMID 24415998PMCID 3874477
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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