Table 1.
Summary of Proteins Involved in Myonuclear Positioning and the Consequences of Their Removal for Muscle Function
| Mammalian | Drosophila | Role in Drosophila | Muscle function consequences (human diseasea; Drosophila) | Refs |
|---|---|---|---|---|
| Nesprin-4 | Klarsicht/Klar | Cooperates with Bocks; cluster formation (separation of nuclei into distinct clusters); myonuclear dispersion (sarcomere assembly); myonuclear spacing and anchoring (regulates myonuclear distances to the NMJ and near the MTJ) | EDMD; affects larval muscle function | [17,18,31,57] |
| Emerin | Bocksbeutel/ Bocks | Cooperates with Klar; cluster formation (separation of nuclei into distinct clusters); cluster spread (viathe cortical pulling pathway); myonuclear spacing and anchoring (in combination with Ote, it regulates Klar expression at the NE; regulates astral MTs) | EDMD; affects larval muscle function | [17,18] |
| SUN2 | Klaroid/Koi | Cluster formation (separation of nuclei into distinct clusters); clusterspread; myonuclear dispersion (sarcomere assembly; regulates Klar expression at the NE) | EDMD disease modifier | [18,31,32,61] |
| Amphiphysin | Amphiphysin/ Amph | Cluster formation (maintains nuclei within clusters); myonuclear spacing and anchoring (necessary for the proper localization of Ma2/d; regulates astral MTs) | CNM; affects larval muscle function | [17,49] |
| MAP7 | Ensconsin/Ens | Positively regulated by Bsg25D; cluster formation; cluster spread; myonuclearspacing and anchoring | Affects larval muscle function | [15,19] |
| Ninein | Blastoderm-specific gene 25D/Bsg25D | Positively regulates Ens; cluster formation; cluster spread; myonuclear spacing and anchoring (regulate astral MTs and MT stability) | Affects larval muscle stiffness and function | [19] |
| Kinesin/Kif5b | Kinesin/Khc | Cluster spread (force exertion of nuclei leading edge and viathe cortical pulling pathway); myonuclear spacing and anchoring (regulates myonuclear distance near the NMJ) | Not reported | [24,25,57] |
| Dynein | Dynein/Dhc | Cluster spread (force exertion of the nuclear lagging edge and via the cortical pulling pathway); myonuclearspacing and anchoring (regulates myonuclear distance near the NMJ) | Affects larval muscle function | [24,25,57] |
| CLIP1/2 | CLIP-190 | Cluster spread (via the cortical pulling pathway; connects the MTs to the cell cortex) | Affects larval muscle function | [24–26] |
| Dynactin 1, p150 subunit | Glued/p150 | Cluster spread (via the cortical pulling pathway; forms acomplexwith Dynein) | Affects larval muscle function | [24,25] |
| G protein-signaling modulator 2 | Partner of inscuteable/pins/raps | Cluster spread (via the cortical pulling pathway; anchors Dynein at the muscle ends); myonuclear spacing and anchoring (regulates the myonuclear position near the MTJ) | Not reported | [26,57] |
| JIP3 | Sunday driver/Syd | Cluster spread (via the cortical pulling pathway; mediates the formation of a Kinesin-Dynein complex) | Affects larval muscle function | [26] |
| JIP1 | Aplip1 | Cluster spread (regulates nuclear translocation via changes in nuclear shape and the cortical pulling pathway; regulates the MT networks) | Not reported | [27] |
| SYNE-1/SYNE-2 | Muscle-specific protein 300 kDa/ MSP-300 | Myonuclear spacing and anchoring (provides elasticity to the perinuclear shield; maintenance of nuclear shape; attachment of the MT asters to the NE; necessary for the proper localization of Ma2/d) | Autosomal-dominant EDMD, EDMD-like phenotypes, arthrogryposis (SYNE-1), autosomal recessive cerebellar ataxia type 1 (SYNE-1); affects larval muscle function, control of glutamate receptor density at the NMJ | [31,49,62] |
| Spectraplakin | Short stop/ Shot | Myonuclear spacing and anchoring (provides rigidity to the perinuclear shield) | Not reported | [48] |
| EB family member 1 | Eb1 | Myonuclear spacing and anchoring (provides rigidity to the perinuclear shield) | Not reported | [48] |
| Emerin | Otefin/Ote | Myonuclear spacing and anchoring (in combination with bocks, it regulates klar expression at the NE) | X-EDMD | [18,63] |
| Muscle-specific α2/δ/Ma2/d | Myonuclear spacing and anchoring (necessary for the sarcoplasmic reticulum-nucleus association) | Affects larval muscle function | [49] | |
| ARIH1 | Ariadne 1/ Ari-1 | Myonuclear spacing and anchoring (proper localization of MSP-300; mono-ubiquitinates Koi) | SMC dysfunction (e.g., thoracic aortic aneurysms) | [50,51] |
a
Where known.