| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-86 |
Sentence |
denotes |
Disease-associated mutations in human BICD2 hyperactivate motility of dynein-dynactin. |
| T2 |
87-201 |
Sentence |
denotes |
Bicaudal D2 (BICD2) joins dynein with dynactin into a ternary complex (termed DDB) capable of processive movement. |
| T3 |
202-367 |
Sentence |
denotes |
Point mutations in the BICD2 gene have been identified in patients with a dominant form of spinal muscular atrophy, but how these mutations cause disease is unknown. |
| T4 |
368-514 |
Sentence |
denotes |
To investigate this question, we have developed in vitro motility assays with purified DDB and BICD2's membrane vesicle partner, the GTPase Rab6a. |
| T5 |
515-668 |
Sentence |
denotes |
Rab6a-GTP, either in solution or bound to artificial liposomes, released BICD2 from an autoinhibited state and promoted robust dynein-dynactin transport. |
| T6 |
669-756 |
Sentence |
denotes |
In these assays, BICD2 mutants showed an enhanced ability to form motile DDB complexes. |
| T7 |
757-877 |
Sentence |
denotes |
Increased retrograde transport by BICD2 mutants also was observed in cells using an inducible organelle transport assay. |
| T8 |
878-980 |
Sentence |
denotes |
When overexpressed in rat hippocampal neurons, the hyperactive BICD2 mutants decreased neurite growth. |
| T9 |
981-1193 |
Sentence |
denotes |
Our results reveal that dominant mutations in BICD2 hyperactivate DDB motility and suggest that an imbalance of minus versus plus end-directed microtubule motility in neurons may underlie spinal muscular atrophy. |
