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N-Terminal signal sequence is required for cellular trafficking and hyaluronan-depolymerization of KIAA1199.

N-Terminal signal sequence is required for cellular trafficking and hyaluronan-depolymerization of KIAA1199.

FEBS letters (2013-11-26)

Hiroyuki Yoshida, Aya Nagaoka, Sachiko Nakamura, Megumi Tobiishi, Yoshinori Sugiyama, Shintaro Inoue

摘要

Recently, we disclosed that KIAA1199-mediated hyaluronan (HA) depolymerization requires an acidic cellular microenvironment (e.g. clathrin-coated vesicles or early endosomes), but no information about the structural basis underlying the cellular targeting and functional modification of KIAA1199 was available. Here, we show that the cleavage of N-terminal 30 amino acids occurs in functionally matured KIAA1199, and the deletion of the N-terminal portion results in altered intracellular trafficking of the molecule and loss of cellular HA depolymerization. These results suggest that the N-terminal portion of KIAA1199 functions as a cleavable signal sequence required for proper KIAA1199 translocation and KIAA1199-mediated HA depolymerization.

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