---
pmid: '22647598'
title: Myotubularin-related protein (MTMR) 9 determines the enzymatic activity, substrate
  specificity, and role in autophagy of MTMR8.
authors:
- Zou J
- Zhang C
- Marjanovic J
- Kisseleva MV
- Majerus PW
- Wilson MP
journal: Proc Natl Acad Sci U S A
year: '2012'
full_text_available: false
pmcid: PMC3386095
doi: 10.1073/pnas.1207021109
pubmed_publication_types:
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
publication_type: PRIMARY_RESEARCH
---

# Myotubularin-related protein (MTMR) 9 determines the enzymatic activity, substrate specificity, and role in autophagy of MTMR8.
**Authors:** Zou J, Zhang C, Marjanovic J, Kisseleva MV, Majerus PW, Wilson MP
**Journal:** Proc Natl Acad Sci U S A (2012)
**DOI:** [10.1073/pnas.1207021109](https://doi.org/10.1073/pnas.1207021109)
**PMC:** [PMC3386095](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386095/)

## Abstract

1. Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9539-44. doi:
10.1073/pnas.1207021109. Epub 2012 May 30.

Myotubularin-related protein (MTMR) 9 determines the enzymatic activity,
substrate specificity, and role in autophagy of MTMR8.

Zou J(1), Zhang C, Marjanovic J, Kisseleva MV, Majerus PW, Wilson MP.

Author information:
(1)Department of Pathology and Immunology, Washington University School of
Medicine, St Louis, MO 63110, USA.

The myotubularins are a large family of inositol polyphosphate 3-phosphatases
that, despite having common substrates, subsume unique functions in cells that
are disparate. The myotubularin family consists of 16 different proteins, 9
members of which possess catalytic activity, dephosphorylating
phosphatidylinositol 3-phosphate [PtdIns(3)P] and phosphatidylinositol
3,5-bisphosphate [PtdIns(3,5)P(2)] at the D-3 position. Seven members are
inactive because they lack the conserved cysteine residue in the CX(5)R motif
required for activity. We studied a subfamily of homologous myotubularins,
including myotubularin-related protein 6 (MTMR6), MTMR7, and MTMR8, all of which
dimerize with the catalytically inactive MTMR9. Complex formation between the
active myotubularins and MTMR9 increases their catalytic activity and alters
their substrate specificity, wherein the MTMR6/R9 complex prefers
PtdIns(3,5)P(2) as substrate; the MTMR8/R9 complex prefers PtdIns(3)P. MTMR9
increased the enzymatic activity of MTMR6 toward PtdIns(3,5)P(2) by over
30-fold, and enhanced the activity toward PtdIns(3)P by only 2-fold. In
contrast, MTMR9 increased the activity of MTMR8 by 1.4-fold and 4-fold toward
PtdIns(3,5)P(2) and PtdIns(3)P, respectively. In cells, the MTMR6/R9 complex
significantly increases the cellular levels of PtdIns(5)P, the product of
PI(3,5)P(2) dephosphorylation, whereas the MTMR8/R9 complex reduces cellular
PtdIns(3)P levels. Consequentially, the MTMR6/R9 complex serves to inhibit
stress-induced apoptosis and the MTMR8/R9 complex inhibits autophagy.

DOI: 10.1073/pnas.1207021109
PMCID: PMC3386095
PMID: 22647598 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no conflict of interest.