KASH 'n Karry: The KASH domain family of cargo‐specific cytoskeletal adaptor proteins

Starr, Daniel A.; Fischer, Janice A.

doi:10.1002/bies.20312

Cited by 148 publications

(198 citation statements)

References 68 publications

(108 reference statements)

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“…The klarsicht gene was found to encode a protein with a Cterminal domain shared with ANC-1 of C. elegans and Syne/Nesprin proteins of vertebrates (Starr and Fischer, 2005;Wilhelmsen et al, 2006). This motif was termed the KASH domain for Klarsicht, ANC-1, and Syne homology.…”

Section: Linking the Nucleus To The Cytoskeletonmentioning

confidence: 99%

“…Specifically, mutational screens in yeast (Saccharomyces cervisiae and Schizoscharomyces pombe), filamentous fungi (Aspergillus nidulins and Neurospora crassa), nematodes (Caenorhadbitis elegans), and fruit flies (Drosophila melanogaster) have all implicated microtubule-based motors and specific classes of nuclear envelope proteins as essential for nuclear migration and positioning (Morris, 2003;Xiang and Fischer, 2004;Starr and Fischer, 2005;Wilhelmsen et al, 2006). With regard to cytoskeletal motors, cytoplasmic dynein and dynactin are essential for normal nuclear migration in multiple contexts.…”

Section: Proteins For Movingmentioning

confidence: 99%

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Nuclear migration during retinal development

2008

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In this review we focus on the mechanisms, regulation, and cellular consequences of nuclear migration in the developing retina. In the nervous system, nuclear migration is prominent during both proliferative and post-mitotic phases of development. Interkinetic nuclear migration is the process where the nucleus oscillates from the apical to basal surfaces in proliferative neuroepithelia. Proliferative nuclear movement occurs in step with the cell cycle, with M-phase being confined to the apical surface and G1-, S-, and G2-phases occurring at more basal locations. Later, following cell cycle exit, some neuron precursors migrate by nuclear translocation. In this mode of cellular migration, nuclear movement is the driving force for motility. Following discussion of the key components and important regulators for each of these processes, we present an emerging model where interkinetic nuclear migration functions to distinguish cell fates among retinal neuroepithelia. Keywordsinterkinetic nuclear migration; nuclear translocation; nucleokinesis; neurogenesis; dynein; cell cycle; cell behavior OverviewNeuronal development is regulated by a complex array of intrinsic and extrinsic signals that act on progenitor neuroepithelial cells to ensure the correct cell type is generated in the right numbers and at the appropriate time of development (Donovan et al., 2005;Cayouette et al., 2006). In addition, multiple signaling cues are integrated in post-mitotic neuronal precursors to facilitate directed cell migration and correct laminar positioning (Malicki et al., 2004). This spatial and temporal regulation of neuronal cell-type fate commitment and histogenesis is dependent on the regulation of the mitotic cell cycle, and in particular at the level of cell cycle exit (Ohnuma and Harris, 2003). Recent data suggest that nuclear migration is a critical process for several aspects of neuronal development, including that of the neural retina. The focus of this review is on interkinetic nuclear migration and nuclear translocation during retinogenesis, although much of what we know is from observations in other regions of the developing nervous system. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript Interkinetic nuclear migrationInterkinetic nuclear migration is the proliferative cell behavior where the nuclei of neuroepithelial cells migrate in an apical-basal manner and in phase with the cell cycle (Frade 2002). Neuroepithelial cell divisions are confined to apical locations while S-phase occu...

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Section: Linking the Nucleus To The Cytoskeletonmentioning

confidence: 99%

Section: Proteins For Movingmentioning

confidence: 99%

Nuclear migration during retinal development

2008

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“…2; for review see 6,[13][14][15]. In general, SUN proteins contain a conserved SUN domain at their C-termini and at least one transmembrane domain.…”

Section: Kash and Sun Proteins Bridge The Nuclear Envelopementioning

confidence: 99%

“…2; for review see ref. 6,[13][14][15]. The nuclear envelope bridging model has been refined by four groups who have each concluded that SUN proteins reside in the INM where they function to target and retain KASH proteins to the ONM through a direct interaction.…”

Section: Kash and Sun Proteins Bridge The Nuclear Envelopementioning

confidence: 99%

Communication between the cytoskeleton and the nuclear envelope to position the nucleus

Starr

2007

Mol. BioSyst.

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In most eukaryotic cells, the nucleus is localized to a specific location. This highlight article focuses on recent advances describing the mechanisms of nuclear migration and anchorage. Central to nuclear positioning mechanisms is the communication between the nuclear envelope and the cytoskeleton. All three components of the cytoskeleton-microtubules, actin filaments and intermediate filaments -are involved in nuclear positioning to varying degrees in different cell types. KASH proteins on the outer nuclear membrane connect to SUN proteins on the inner nuclear membrane. Together they transfer forces between the cytoskeleton and the nuclear lamina. Once at the outer nuclear membrane, KASH proteins can interact with the cytoskeleton. Nuclear migrations are a component of many cellular migration events and defects in nuclear positioning lead to human diseases, most notably lissencephaly.

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“…Although UNC-83 is essential for nuclear migration in many developmental events, its molecular mechanism and interacting partners remain unknown. UNC-84 is a novel protein with a (Hagan and Yanmagida, 1995;Malone et al, 1999Malone et al, , 2003Hodzic et al, 2004;Padmakumar et al, 2005;Starr and Fischer, 2005). UNC-84 localizes to the nuclear envelope in nearly all somatic cells from the 24-cell stage on in development .…”

mentioning

confidence: 99%

UNC-83 Is a KASH Protein Required for Nuclear Migration and Is Recruited to the Outer Nuclear Membrane by a Physical Interaction with the SUN Protein UNC-84

McGee

Rillo

Anderson

et al. 2006

MBoC

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UNC-84 is required to localize UNC-83 to the nuclear envelope where it functions during nuclear migration. A KASH domain in UNC-83 was identified. KASH domains are conserved in the nuclear envelope proteins Syne/nesprins, Klarsicht, MSP-300, and ANC-1. Caenorhabditis elegans UNC-83 was shown to localize to the outer nuclear membrane and UNC-84 to the inner nuclear membrane in transfected mammalian cells, suggesting the KASH and SUN protein targeting mechanisms are conserved. Deletion of the KASH domain of UNC-83 blocked nuclear migration and localization to the C. elegans nuclear envelope. Some point mutations in the UNC-83 KASH domain disrupted nuclear migration, even if they localized normally. At least two separable portions of the C-terminal half of UNC-84 were found to interact with the UNC-83 KASH domain in a membrane-bound, split-ubiquitin yeast two-hybrid system. However, the SUN domain was essential for UNC-84 function and UNC-83 localization in vivo. These data support the model that KASH and SUN proteins bridge the nuclear envelope, connecting the nuclear lamina to cytoskeletal components. This mechanism seems conserved across eukaryotes and is the first proposed mechanism to target proteins specifically to the outer nuclear membrane. INTRODUCTIONA variety of cellular and developmental processes, including fertilization, cell division, cell migration, and establishment of polarity, depend on positioning the nucleus to a specific location within the cell. For example, in budding yeast the nucleus must migrate to the bud neck before the onset of mitosis. Also, nuclei actively follow the leading edge of migratory cells, such as those in the developing cerebral cortex. Nuclear migration defects in these two examples lead to the missegregation of chromosomes or the neurological disease lissencephaly, respectively (reviewed in Morris, 2000). The role of microtubules and associated dynein and kinesin motors in nuclear migration are well established (reviewed in Reinsch and Gonczy, 1998). Although less established, actin also plays an important role in many nuclear positioning events (reviewed in Starr and Han, 2003). Recently, a definitive role for actin networks has been described in nuclear migration during NIH 3T3 cell polarization (Gomes et al., 2005). It remains relatively unknown how the nucleus connects to the cytoplasmic cytoskeleton during nuclear migration. Furthermore, it is not clear how the forces involved in nuclear positioning are transferred across both membranes of the nuclear envelope from the cytoskeleton to the nuclear matrix.We have previously proposed that two C. elegans proteins, UNC-84 and UNC-83, function to control nuclear migration by bridging the nuclear envelope, connecting the cytoskeleton with the nuclear matrix (Starr et al., 2001;Lee et al., 2002;Starr and Han, 2003). Mutations in unc-83 or unc-84 disrupt nuclear migration in at least three cell types: embryonic hypodermal hyp7 precursors, larval hypodermal P-cells, and embryonic intestinal primordial cells (Horvitz and Sulst...

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KASH 'n Karry: The KASH domain family of cargo‐specific cytoskeletal adaptor proteins

Cited by 148 publications

References 68 publications

Nuclear migration during retinal development

Nuclear migration during retinal development

Communication between the cytoskeleton and the nuclear envelope to position the nucleus

UNC-83 Is a KASH Protein Required for Nuclear Migration and Is Recruited to the Outer Nuclear Membrane by a Physical Interaction with the SUN Protein UNC-84

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