Asymmetic Localization
In both invertebrates and mammals, Numb is localized using the Pins/GαI complex and the PAR complex of Bazooka (Par3 in mammals), Par6, and aPKC (atypical protein kinase C). In the sensory organ precursor (SOP) cell, the PAR proteins localize to the posterior pole of the cell, and the Pins/GαI complex is localized to the anterior pole of the cell. This results in an anterior/posterior cell division with daughter cells of similar size. In neuroblasts, both complexes are localized to the apical cortex, causing apical/basal cell division and daughter cells exhibiting strong size asymmetry. In the SOP, one mechanism for Numb localization has been proposed based on the PAR complex. It states that a complex phosphorylation cascade enables aPKC to phosphorylate Numb in the pre-mitotic cell, decreasing its affinity for the plasma membrane. This releases Numb from the aPKC pole, increasing its presence in the non-aPKC pole. This establishes the asymmetric distribution of Numb, with the Numb/Pon crescent on one side of the mother cell.
Another proposed component of the localization complex is Partner of Numb (PON), which is asymmetrically localized during mitosis and acts as an adaptor protein by binding and mediating the anchoring of Numb. The localization of PON is controlled by either Insc or the Frizzled-Wnt signaling pathway.
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