The dilute-lethal (d) gene attacks a Ca2+ store in the dendritic spine of Purkinje cells in mice

Takagishi, Yoshiko; Oda, Sen-ichi; Hayasaka, Shizu; Dekker-Ohno, K.; Shikata, T.; Inouye, Minoru; Yamamura, Hideki

doi:10.1016/0304-3940(96)12967-0

Cited by 141 publications

(99 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The yeast two-hybrid studies suggest that one way this transport is coordinated is through the direct interaction of the different motor molecules. These data are consistent with previous studies, which showed that MyoVa and kinesin both can bind synaptic vesicles in the rat (17,18) and that MyoVa is required for short-range, but not long-range, transport of smooth endoplasmic reticulum in Purkinje cells (9,10).…”

supporting

confidence: 93%

See 1 more Smart Citation

A mutation in Rab27a causes the vesicle transport defects observed in ashen mice

Wilson

Yip

Swing

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

381

363

View full text Add to dashboard Cite

The dilute (d), leaden (ln), and ashen (ash) mutations provide a unique model system for studying vesicle transport in mammals. All three mutations produce a lightened coat color because of defects in pigment granule transport. In addition, all three mutations are suppressed by the semidominant dilute-suppressor (dsu), providing genetic evidence that these mutations function in the same or overlapping transport pathways. Previous studies showed that d encodes a major vesicle transport motor, myosin-VA, which is mutated in Griscelli syndrome patients. Here, using positional cloning and bacterial artificial chromosome rescue, we show that ash encodes Rab27a. Rab GTPases represent the largest branch of the p21 Ras superfamily and are recognized as key players in vesicular transport and organelle dynamics in eukaryotic cells. We also show that ash mice have platelet defects resulting in increased bleeding times and a reduction in the number of platelet dense granules. These defects have not been reported for d and ln mice. Collectively, our studies identify Rab27a as a critical gene for organelle-specific protein trafficking in melanocytes and platelets and suggest that Rab27a functions in both MyoVa dependent and independent pathways.

show abstract

supporting

confidence: 93%

“…The neurological defect is thought to result from the failure to transport smooth endoplasmic reticulum (SER) from the dendritic shaft to the dendritic spines of cerebellar Purkinje cells (9,10). The absence of SER in spines probably disrupts the regulation of intracellular Ca 2ϩ and postsynaptic signal transduction.…”

mentioning

confidence: 99%

A mutation in Rab27a causes the vesicle transport defects observed in ashen mice

Wilson

Yip

Swing

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

381

363

View full text Add to dashboard Cite

show abstract

“…Our kinetic study demonstrated that myosin Vc is a low duty ratio motor. Consistently, the single molecule assays of total internal reflection fluorescence (TIRF) 3 microscopy revealed that myosin Vc does not move processively on actin filaments. It is thought that myosin Vc serves as a membrane transporter in cells, but our results suggests that it would be achieved by a quite different mechanism from myosin Va and Vb.…”

mentioning

confidence: 67%

“…Class V myosins have been widely found in species from lower organisms, such as yeast, Caenorhabditis elegans, and Drosophila, to vertebrates. In vertebrates, there are three distinct subclasses of myosin V. Among them, most of the research has focused on myosin Va, which plays a critical role in membrane trafficking, including melanosome transport (1,2) and endoplasmic reticulum transport (3)(4)(5)(6). In contrast to myosin Va expressed mainly in brain and melanocytes, myosin Vb and Vc are widely expressed in a variety of tissues, although the relative expression level is distinct from each other.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Human Myosin Vc Is a Low Duty Ratio Nonprocessive Motor

Watanabe

Satō

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

There are three distinct members of the myosin V family in vertebrates, and each isoform is involved in different membrane trafficking pathways. Both myosin Va and Vb have demonstrated that they are high duty ratio motors that are consistent with the processive nature of these motors. Here we report that the ATPase cycle mechanism of the single-headed construct of myosin Vc is quite different from those of other vertebrate myosin V isoforms. K ATPase of the actin-activated ATPase was 62 M, which is much higher than that of myosin Va (ϳ1 M). The rate of ADP release from actomyosin Vc was 12.7 s ؊1 , which was 2 times greater than the entire ATPase cycle rate, 6.5 s ؊1 . P i burst size was 0.31, indicating that the equilibrium of the ATP hydrolysis step is shifted to the prehydrolysis form. Our kinetic model, based on all kinetic data we determined in this study, suggests that myosin Vc spends the majority of the ATPase cycle time in the weak actin binding state in contrast to myosin Va and Vb. Consistently, the two-headed myosin Vc construct did not show processive movement in total internal reflection fluorescence microscope analysis, demonstrating that myosin Vc is a nonprocessive motor. Our findings suggest that myosin Vc fulfills its function as a cargo transporter by different mechanisms from other myosin V isoforms.Class V myosins function as actin-based motors for various cargo transportations. Class V myosins have been widely found in species from lower organisms, such as yeast, Caenorhabditis elegans, and Drosophila, to vertebrates. In vertebrates, there are three distinct subclasses of myosin V. Among them, most of the research has focused on myosin Va, which plays a critical role in membrane trafficking, including melanosome transport (1, 2) and endoplasmic reticulum transport (3-6). In contrast to myosin Va expressed mainly in brain and melanocytes, myosin Vb and Vc are widely expressed in a variety of tissues, although the relative expression level is distinct from each other. For instance, myosin Vb is most abundant in kidney, whereas myosin Vc is significantly expressed in epithelial and glandular tissues, including pancreas, colon, and stomach (7).Evidence has shown that myosin V is a cargo transporter and serves as a membrane transporter in various biological processes. Myosin Va is involved in melanosome transportation in melanocytes (1, 2) and synaptic vesicle movement in neuronal cells (3-6). On the other hand, myosin Vb is involved in the plasma membrane recycling systems of transferrin receptor (8), chemokine receptor CXCR2 (9), and M4 muscarinic acetylcholine receptor (10). Although the tissue distribution of the expression of myosin Vb and Vc is overlapped, it is thought that they have a distinct physiological relevance. Myosin Vb directly interacts with the small GTP-binding protein, Rab11a (8), whereas myosin Vc colocalizes with Rab8, but not Rab11a (7), suggesting that each myosin V isoform has specific target cargo molecules and is involved in different membrane trafficking pathways.Th...

show abstract

Vesicle transport: The role of actin filaments and myosin motors

DePina

Langford

1999

Microsc. Res. Tech.

136

View full text Add to dashboard Cite

The transport of vesicles and the retention of organelles at specific locations are fundamental processes in cells. Actin filaments and myosin motors have been shown to be required for both of these tasks. Most of the organelles in cells associate with actin filaments and some of the myosin motors required for movement on actin filaments have been identified. Myosin V has been shown to transport endoplasmic reticulum (ER) vesicles in neurons, pigment granules in melanocytes, and the vacuole in yeast. Myosin I has been shown to be involved in the transport of Golgi‐derived vesicles in epithelial cells. Myosin VI has been shown to be associated with Golgi‐derived vesicles, and cytoplasmic vesicles in living Drosophila embryos. Myosin II may be a vesicle motor but its role in vesicle transport has not been resolved. Secretory vesicles, endosomes and mitochondria appear to be transported on actin filaments but the myosin motors on these organelles have not been identified. Mitochondria in yeast may be transported by the dynamic assembly of an actin “tail.” The model that has unified all of these findings is the concept that long‐range movement of vesicles occurs on microtubules and short‐range movement on actin filaments. The details of how the microtubule‐dependent and the actin‐dependent motors are coordinated are important questions in the field. There is now strong evidence that two molecular motors, kinesin and myosin V, interact with each other and perhaps function as a complex on vesicles. An understanding of the interrelationship of microtubules and actin filaments and the motors that move cargo on them will ultimately establish how vesicles and organelles are transported to their specific locations in cells. Microsc. Res. Tech. 47:93–106, 1999. © 1999 Wiley‐Liss, Inc.

show abstract

The dilute-lethal (d) gene attacks a Ca2+ store in the dendritic spine of Purkinje cells in mice

Cited by 141 publications

References 19 publications

A mutation in Rab27a causes the vesicle transport defects observed in ashen mice

A mutation in Rab27a causes the vesicle transport defects observed in ashen mice

Human Myosin Vc Is a Low Duty Ratio Nonprocessive Motor

Vesicle transport: The role of actin filaments and myosin motors

Contact Info

Product

Resources

About