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• W2044002783 abstract "Matrix metalloproteases (MMPs) are endopeptidases that regulate diverse biological processes. Synthesized as zymogens, MMPs become active after removal of their prodomains. Much is known about the metalloprotease activity of these enzymes, but noncanonical functions are poorly defined, and functions of the prodomains have been largely ignored. Here we report a novel metalloprotease-independent, channel-modulating function for the prodomain of MMP23 (MMP23-PD). Whole-cell patch clamping and confocal microscopy, coupled with deletion analysis, demonstrate that MMP23-PD suppresses the voltage-gated potassium channel KV1.3, but not the closely related KV1.2 channel, by trapping the channel intracellularly. Studies with KV1.2-1.3 chimeras suggest that MMP23-PD requires the presence of the KV1.3 region from the S5 trans-membrane segment to the C terminus to modulate KV1.3 channel function. NMR studies of MMP23-PD reveal a single, kinked trans-membrane α-helix, joined by a short linker to a juxtamembrane α-helix, which is associated with the surface of the membrane and protected from exchange with the solvent. The topological similarity of MMP23-PD to KCNE1, KCNE2, and KCNE4 proteins that trap KV1.3, KV1.4, KV3.3, and KV3.4 channels early in the secretory pathway suggests a shared mechanism of channel regulation. MMP23 and KV1.3 expression is enhanced and overlapping in colorectal cancers where the interaction of the two proteins could affect cell function.Background: Noncanonical functions of matrix metalloproteases are poorly characterized.Results: The prodomain of MMP23 co-localizes with and traps KV1.3 channels intracellularly, thereby suppressing KV1.3 currents.Conclusion: A novel metalloprotease-independent channel-modulating function of the MMP23 prodomain has been identified.Significance: The topological similarity of the prodomain of MMP23 and KCNE proteins suggests a shared mechanism of channel modulation. Matrix metalloproteases (MMPs) are endopeptidases that regulate diverse biological processes. Synthesized as zymogens, MMPs become active after removal of their prodomains. Much is known about the metalloprotease activity of these enzymes, but noncanonical functions are poorly defined, and functions of the prodomains have been largely ignored. Here we report a novel metalloprotease-independent, channel-modulating function for the prodomain of MMP23 (MMP23-PD). Whole-cell patch clamping and confocal microscopy, coupled with deletion analysis, demonstrate that MMP23-PD suppresses the voltage-gated potassium channel KV1.3, but not the closely related KV1.2 channel, by trapping the channel intracellularly. Studies with KV1.2-1.3 chimeras suggest that MMP23-PD requires the presence of the KV1.3 region from the S5 trans-membrane segment to the C terminus to modulate KV1.3 channel function. NMR studies of MMP23-PD reveal a single, kinked trans-membrane α-helix, joined by a short linker to a juxtamembrane α-helix, which is associated with the surface of the membrane and protected from exchange with the solvent. The topological similarity of MMP23-PD to KCNE1, KCNE2, and KCNE4 proteins that trap KV1.3, KV1.4, KV3.3, and KV3.4 channels early in the secretory pathway suggests a shared mechanism of channel regulation. MMP23 and KV1.3 expression is enhanced and overlapping in colorectal cancers where the interaction of the two proteins could affect cell function. Background: Noncanonical functions of matrix metalloproteases are poorly characterized. Results: The prodomain of MMP23 co-localizes with and traps KV1.3 channels intracellularly, thereby suppressing KV1.3 currents. Conclusion: A novel metalloprotease-independent channel-modulating function of the MMP23 prodomain has been identified. Significance: The topological similarity of the prodomain of MMP23 and KCNE proteins suggests a shared mechanism of channel modulation." @default.
• W2044002783 created "2016-06-24" @default.
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• W2044002783 date "2013-03-01" @default.
• W2044002783 modified "2023-10-07" @default.
• W2044002783 title "Intracellular Trafficking of the KV1.3 Potassium Channel Is Regulated by the Prodomain of a Matrix Metalloprotease" @default.
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• W2044002783 cites W1966078827 @default.
• W2044002783 cites W1967849828 @default.
• W2044002783 cites W1972772995 @default.
• W2044002783 cites W1987634654 @default.
• W2044002783 cites W1995688871 @default.
• W2044002783 cites W1997543160 @default.
• W2044002783 cites W1999663172 @default.
• W2044002783 cites W2001075788 @default.
• W2044002783 cites W2002771508 @default.
• W2044002783 cites W2005986251 @default.
• W2044002783 cites W2006715336 @default.
• W2044002783 cites W2007200306 @default.
• W2044002783 cites W2009667219 @default.
• W2044002783 cites W2016433313 @default.
• W2044002783 cites W2019737005 @default.
• W2044002783 cites W2022760884 @default.
• W2044002783 cites W2024211926 @default.
• W2044002783 cites W2028277256 @default.
• W2044002783 cites W2031282085 @default.
• W2044002783 cites W2033458525 @default.
• W2044002783 cites W2035266068 @default.
• W2044002783 cites W2040731493 @default.
• W2044002783 cites W2051864856 @default.
• W2044002783 cites W2054439861 @default.
• W2044002783 cites W2057477511 @default.
• W2044002783 cites W2062746203 @default.
• W2044002783 cites W2063948774 @default.
• W2044002783 cites W2065554849 @default.
• W2044002783 cites W2066015352 @default.
• W2044002783 cites W2071359561 @default.
• W2044002783 cites W2079407305 @default.
• W2044002783 cites W2083849026 @default.
• W2044002783 cites W2086862822 @default.
• W2044002783 cites W2089719502 @default.
• W2044002783 cites W2092508662 @default.
• W2044002783 cites W2105318310 @default.
• W2044002783 cites W2106335202 @default.
• W2044002783 cites W2112418305 @default.
• W2044002783 cites W2113668309 @default.
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• W2044002783 doi "https://doi.org/10.1074/jbc.m112.421495" @default.
• W2044002783 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3585079" @default.
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