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Fig. 6 | Molecular Brain

Fig. 6

From: Non-SUMOylated CRMP2 decreases NaV1.7 currents via the endocytic proteins Numb, Nedd4-2 and Eps15

Fig. 6

Schematic representation of CRMP2 regulation of NaV1.7 channels. Top: In wildtype (WT) mice (left), when CRMP2 is SUMOylated it interacts with NaV1.7 channels to enhance their trafficking to the plasma membrane. In CRMP2K374A/K374A mice (right), non-SUMOylated CRMP2 recruits Numb, Nedd4-2 and Eps15 to trigger clathrin-mediated endocytosis of NaV1.7 channels. Bottom: Sex specific differences of female (left) and male (right) CRMP2K374A/K374A mice compared to their WT littermates. In female mice: (i) NaV1.7 membrane expression, currents, and CRMP2-NaV1.7 interaction are reduced [37], (ii) Pitstop2 restores the loss of sodium currents and allodynia [37], (iii) in basal conditions no difference in the expression of endocytic proteins is seen and, (iv) silencing Numb, Nedd4-2 and Eps15 restores the loss of sodium currents. In male mice: (i) NaV1.7 membrane expression, currents, and CRMP2-NaV1.7 interaction are not modified [37], (ii) Pitstop2 has no effect on sodium currents (37) but restores mechanical allodynia, and (iii) in basal conditions no difference in the expression of Numb, Nedd4-2 and Eps15 is observed. Red text represents the data obtained in this study

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