Switch #:
SWTI000672
Switch type:
Binary
Switch subtype:
Pre-translational

Description:
Alternative splicing removes the Kinesin Light Chain-binding motif of Pleckstrin homology domain-containing family M member 2 (PLEKHM2), abrogating binding to Kinesin light chain 2 (KLC2). Pleckstrin homology domain-containing family M member 2 (PLEKHM2) contains kinesin light chain (KLC) binding WD motifs (second motif at 205-210), and these are required for kinesin-1 recruitment and the peripheral movement of lysosomes. ADP-ribosylation factor-like protein 8B (ARL8B) and PLEKHM2 act together to recruit kinesin-1 to lysosomes and hence direct their movement toward microtubule plus ends. A splice variant of PLEKHM2 that lacks a light chain binding motif does not stimulate movement, suggesting fine-tuning by alternative splicing.

Participants:
(1) Pleckstrin homology domain-containing family M member 2 (PLEKHM2)
(2) Kinesin light chain 2 (KLC2)

Interactions
Interaction #1 PLEKHM2 - KLC2

Interfaces
(1) ELM:LIG_TPR_Kinesin_1 motif (236WEDGD240) in Pleckstrin homology domain-containing family M member 2 (PLEKHM2)
(2) Tetratricopeptide repeat (198-482) in Kinesin light chain 2 (KLC2)

Interaction Regulation
Alternative splicing Abrogation of the Pleckstrin homology domain-containing family M member 2 (PLEKHM2) LIG_TPR_Kinesin_1 motif - Kinesin light chain 2 (KLC2) Tetratricopeptide repeat interaction

References

(1) Arl8 and SKIP act together to link lysosomes to kinesin-1.
Rosa-Ferreira et al. Dev. Cell (2011)




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